Meryl Streep, an actress with a career spanning over four decades and a record 21 Academy Award nominations, guest-starred in "The Simpsons" in the episode "Bart's Girlfriend" in season 6. She voiced Jessica Lovejoy, the rebellious daughter of Reverend Lovejoy. Jessica becomes the object of Bart's affection, leading to a storyline filled with young love, mischief, and a surprising twist. Streep's nuanced performance added depth to Jessica's character, making her one of the most memorable guest characters in the series.

Danny DeVito, an actor known for his distinctive comedic style and memorable roles in films like "Twins" and "Matilda," played Herbert Powell, Homer's long-lost half-brother, in the episode "Oh Brother, Where Art Thou?" in season 2. DeVito's character, a wealthy head of Powell Motors, adds a new dynamic to the Simpson family dynamics. DeVito's performance brought a unique blend of humor and pathos to the character, making Herbert's storyline one of the most engaging in the series.

In the episode "Deep Space Homer" from season 5, American astronaut Buzz Aldrin, the second man to walk on the moon, guest-starred alongside musician James Taylor. The episode, which sees Homer selected by NASA for a space exploration project, is a hilarious take on space travel and the celebrity status of astronauts. Aldrin's appearance added a touch of authenticity to the episode, and his good-natured participation in the show's humor made it a standout entry in the series.

Leonard Nimoy, best known for his iconic role as Spock in the "Star Trek" franchise, appeared as himself in the episode "The Springfield Files" in season 8. The episode, which parodies "The X Files," sees Homer claiming to have discovered an alien in Springfield. Nimoy's guest appearance added a layer of sci-fi credibility to the episode, and his willingness to poke fun at his Spock persona made for some of the show's most memorable moments.

Glenn Close, a highly respected actress known for her roles in films like "Fatal Attraction" and "The Wife," made multiple appearances as Mona Simpson, Homer's mother. Her first appearance was in the episode "Mother Simpson" in season 7, where she played an activist on the run from the law. Close's portrayal of Mona added depth to Homer's character and provided some emotional moments in the series. Her performances were praised for their emotional depth and complexity, making Mona a beloved character in the series.

Acclaimed physicist and author Stephen Hawking made a guest appearance as himself in the episode "They Saved Lisa's Brain" in season 10. The episode sees Lisa recruited by the Springfield chapter of MENSA, leading to a storyline that explores intelligence and societal dynamics. Hawking's appearance was a highlight of the episode, with his sharp wit and self-deprecating humor adding a unique element to the show. His participation in the episode underscored "The Simpsons" ability to blend intellectual humor with popular culture.

The late Stan Lee, the creator of Marvel Comics, made a cameo in the episode "I Am Furious (Yellow)" in season 13. The episode parodies the story of the Hulk and centers around Homer's anger issues. Lee's appearance was a delightful surprise for comic book fans, and his enthusiastic participation in the episode's humor made it a memorable entry in the series. His cameo is a testament to "The Simpsons" broad cultural reach and its ability to attract a wide range of guest stars.

Johnny Cash, the legendary country singer known as "The Man in Black," guest-starred as the Space Coyote in the episode "El Viaje Misterioso de Nuestro Jomer (The Mysterious Voyage of Homer)" in season 8. The episode sees Homer experiencing hallucinations after consuming hot chili peppers, with Cash's character serving as his spirit guide. Cash's deep, resonant voice and his laid-back performance added a surreal and mystical element to the episode, making it one of the most unique and memorable in the series.

Dustin Hoffman, an actor known for his versatile roles in films like "The Graduate" and "Rain Man," appeared in "Lisa's Substitute," the 19th episode of season 2, as Lisa's substitute teacher Mr. Bergstrom. Lisa's teacher ends up taking medical leave and the iconic actor played Lisa's substitute teacher. Students end up loving his teaching style and Lisa is left disappointed when her teacher Miss Hoover returns. Hoffman's sensitive and nuanced performance made Mr. Bergstrom a fan favorite and added a touch of emotional depth to the series.

Anne Hathaway, an Academy Award-winning actress known for her roles in films like "Les Misérables" and "The Devil Wears Prada," guest-starred in the episode "The Good, the Sad and the Drugly" in season 20 as Jenny, a girl who becomes Bart's love interest. Hathaway's character is a charitable and kind-hearted girl who influences Bart to change his ways. Hathaway's performance brought a unique blend of sweetness and sincerity to the character, making her a memorable addition to the series.

Kelsey Grammer, best known for his role as Frasier Crane on "Cheers" and "Frasier," has made multiple appearances as Sideshow Bob, a character who started as Krusty the Clown's sidekick and later became one of the show's most iconic villains. Grammer's theatrical voice and comedic timing have made Sideshow Bob a fan favorite, and his performances have been praised for their blend of humor and menace.

Michelle Pfeiffer, an actress known for her roles in films like "Scarface" and "Dangerous Liaisons," lent her voice to the character of Mindy Simmons in the episode "The Last Temptation of Homer" in season 5. Pfeiffer's character, a beautiful and charming coworker of Homer's, becomes the center of a storyline that explores marital fidelity. Pfeiffer's sultry voice and comedic timing made Mindy a memorable character, and her storyline with Homer is one of the most engaging in the series.

Michael Jackson, the King of Pop, made a guest appearance in the episode "Stark Raving Dad" in season 3, where he voiced a character who believes he is Michael Jackson. The episode is a hilarious and touching exploration of fame and identity, and Jackson's performance added a unique element to the show. His participation in the episode is a testament to "The Simpsons" broad cultural appeal and its ability to attract top-tier talent.

Elizabeth Taylor, one of the last stars of classical Hollywood cinema, guest-starred in the episode "Lisa's First Word" in season 4, where she voiced the character of Maggie Simpson for her first word. Taylor's contribution, though small, is a memorable moment in the series. Her participation in the episode added a touch of Hollywood glamour to the show and underscored "The Simpsons" ability to attract a wide range of guest stars.

Mark Hamill, best known for his role as Luke Skywalker in the "Star Wars" franchise, appeared as himself in the episode "Mayored to the Mob" in season 10. The episode sees Hamill starring in a musical production, leading to a storyline filled with "Star Wars" references and showbiz humor. Hamill's good-natured participation in the episode's humor and his willingness to poke fun at his "Star Wars" persona made it a standout entry in the series.

Alec Baldwin and Kim Basinger, both acclaimed actors in their own right, guest-starred as themselves in the episode "When You Dish Upon a Star" in season 10. The episode sees Homer becoming the personal assistant to the Hollywood couple, leading to a storyline that satirizes celebrity culture. Baldwin and Basinger's performances added a touch of Hollywood glamour to the episode, and their willingness to poke fun at themselves made it a memorable entry in the series.

Paul McCartney, one of the most successful composers and performers of all time, and his then-wife Linda McCartney appeared as themselves in the episode "Lisa the Vegetarian" in season 7. The McCartneys help Lisa become a vegetarian, leading to a storyline that explores the theme of personal beliefs and societal norms. Their participation in the episode added a touch of authenticity to the storyline and underscored "The Simpsons" ability to tackle a wide range of topics.

Patrick Stewart, best known for his roles in "Star Trek: The Next Generation" and the "X-Men" film series, guest-starred as Number One in the episode "Homer the Great" in season 6. Stewart's character is the leader of the Stonecutters, a secret society that Homer joins, leading to a storyline that parodies fraternal organizations. Stewart's commanding voice and comedic timing made his character a memorable addition to the series.

Tom Hanks, one of the most popular and recognizable film stars worldwide, appeared as himself in "The Simpsons Movie." In the film, Hanks endorses the new Grand Canyon in place of Springfield, adding a touch of Hollywood glamour to the movie. Hanks' cameo is a testament to "The Simpsons" broad cultural reach and its ability to attract top-tier talent.

Justin Bieber, a pop star known for his hit songs and his dedicated fan base, made a brief cameo as himself in the episode "The Fabulous Faker Boy" in season 24. Bieber's appearance, though short, is a humorous nod to his pop star status. His cameo is a testament to "The Simpsons" ability to stay relevant and engage with contemporary pop culture.

Ricky Gervais, a comedian known for his acerbic wit and his roles in shows like "The Office" and "Extras," wrote and guest-starred in the episode "Homer Simpson, This Is Your Wife" in season 17. Gervais plays Charles Heathbar, a man who swaps families with Homer as part of a reality show, leading to a storyline that satirizes reality television. Gervais' sharp wit and unique comedic style made the episode a standout entry in the series.

Hugh Hefner, the founder of Playboy magazine, appeared as himself in the episode "Krusty Gets Kancelled" in season 4. Hefner's appearance adds a touch of real-world celebrity to the episode, which sees Krusty the Clown trying to revive his television show. Hefner's cameo is a testament to "The Simpsons" ability to engage with a wide range of cultural figures and its broad cultural appeal.

Lady Gaga, a pop star known for her flamboyant style and hit songs, guest-starred as herself in the episode "Lisa Goes Gaga" in season 23. In the episode, Gaga visits Springfield to help boost the town's morale, leading to a storyline filled with music, spectacle, and self-acceptance. Gaga's performance added a touch of pop star glamour to the episode, and her participation in the show's humor made it a memorable entry in the series.

Stephen King, one of the most famous authors of horror and supernatural fiction, made a guest appearance as himself in the episode "Insane Clown Poppy" in season 12. The episode sees King at a book fair, providing a humorous interaction with the Simpson family. King's cameo is a testament to "The Simpsons" ability to engage with a wide range of cultural figures, and his participation in the episode's humor made it a standout entry in the series.