• Lloyd P. Nebulon (voiced by Courtland Mead) is a 13-year-old Verdigrean. Though he is usually a kind and easygoing teenager, despite his mother's leadership over Intrepidville, he and his group are pegged as "dorks" at Luna Vista Middle School. Such instances involve or result in constant disrespect and occasional bullying at the hands of their classmates, especially ones of the more socially-popular circle. Lloyd has a crush on his classmate Brittany Boviak, a cheerleader who secretly reciprocates his feelings despite bullying him.
• Commander Nora Li Nebulon (voiced by April Winchell) is the commander of Intrepidville and Lloyd and Francine's single mother. She is authoritarian, but patient, caring and supportive.
• Francine Nebulon (voiced by Nicolette Little) is Lloyd's younger sister. She loves her doll Rosie and using her telekinesis and telepathy. Her favorite TV show is The Daisy Droid Girls (a parody of The Powerpuff Girls).
• Station (voiced by Brian George) is the space station's computer. When activated, he assumes the form of an eyeball attached to a long wire leading from a computer terminal. Station has a tendency to be neurotic and dismissive to those around him.
• Edward R. "Eddie" Horton (voiced by Justin Shenkarow) is Lloyd's human best friend. He has wavy orange hair and tries to act in a "cool" manner. His father is a police officer.
• Douglas McNoggin (voiced by Pamela Hayden) is a Cerebellian who resembles a brain with limbs.
• Kurt Blobberts (voiced by Bill Fagerbakke) is Lloyd's large, one-eyed friend of the Blobullon species. While sometimes slow-witted, Kurt is a kind and loving character, but is usually treated the same as the rest of his group of friends. His head can be easily removed from his body and still function well.

• The Zeptar's Bandit (voiced by Danny Cooksey) is a lowly criminal.
• Frontok (voiced by Kevin Michael Richardson) is the captain of a fleet of space pirates.
• The Pick-pocket is a criminal that appears in Eddie's memory in the final episode of the show. He is caught by Eddie's dad.
• Kurtlas is the fusion between Douglas and Kurt due to Lloyd's suggestion. At first, Kurtlas defends the weaker and smaller kids at school from Rodney and the other bullies, but his fame goes to his head and becomes the school bully himself. He is stopped by Lloyd in the end.
• The Preditalien is a monster which attacks and infects Intrepidville from the year X27 to X37. If one scratched or bit another life form they too would become monsters.

• Dunkirque (voiced by Dan Castellaneta) is second-in-command of the space station. He is a tough and obedient prominent aide to Commander Nebulon.
• Larry (voiced by Eddie Deezen) is one of Commander Nebulon's prominent aides. He is a purple humanoid who frequently acts very childishly.
• Boomer (voiced by Diedrich Bader) is the mechanic who repairs all the spacecraft on Intrepidville. He is fairly simple-minded. It is revealed in "Boomer's Secret Life" that he is the heir to his race's throne, but he turned his title over to his brother Sleeveknot.
• Lou 2000 (voiced by John DiMaggio) is Station's bad-mouthed backup system. When in use, he frequently picks on Larry a lot.
• Brittany Boviak (voiced by Anndi McAfee) is a wealthy, popular six-armed Tsktskian girl who is the captain of the cheerleading squad. She is also revealed later in the series to have a secret crush on Lloyd. Although she secretly likes Lloyd, she verbally and emotionally abuses him a lot, giving the impression that he is not worthy of her time.
• Megan Uno (voiced by Rachel Crane) is Brittany's best friend with a single eyestalk. She is usually with Brittany wherever she goes, and most of the time she is slightly more sour than Brittany herself and surprisingly more shallow in terms of boys.
• Cindy (voiced by Tara Strong (right) and Mayim Bialik (left) respectively) is a girl with two heads: one head is friendly, empathetic, and mature, and the other head tends to be rude, offensive, and grouchy. Cindy is one of the few recurring students to be a friend to Lloyd's group.
• Eileen (voiced by Michelle Horn) is a girl who has three eyes and tentacles in place of arms and legs.
• Rodney Glaxer (voiced by Warren Sroka) is a four-armed school bully who is also the quarterback of the Luna Vista crushball team. He favors picking on nerds, particularly Mendel, though he is still often enough antagonistic to anyone of lesser popularity such as Lloyd and his friend group.
• Mendel (voiced by Blake McIver Ewing) is one of the nerds at Luna Vista and the main target of Rodney's bullying. He often hangs out with his nerd friends such as Lou and Benny, as well as other unpopular kids.
• Mrs. Barbara Bolt (voiced by Tress MacNeille) is Lloyd's teacher at Luna Vista Middle School. She is a cranky robot who gets very angry when Lloyd or any other student is messing around in class.
• Mr. Stinko (voiced by Kevin Michael Richardson) is the garbage man of Intrepidville.
• Charmaine is a female Cerebellian. She is seen as a very intelligent character, and often is involved in debates against other schools, often with partner Douglas. She is friends with Douglas, Cindy and Missy.
• Missy is a Blobullon who resembles Kurt in many ways, she has one eye and purple skin. However, she is slightly smaller than Kurt. She and Kurt seem to like each other as shown in "Double Date", he compliments her saying she is "neat". She is friends with Cindy, Charmaine and Kurt.
• Leo Andromedos (voiced by Brian Doyle-Murray) is the grandfather of Lloyd and Francine and the father of Nora. He is a father figure to Lloyd.
• Jake is one of Rodney's friends. Jake, like Rodney, is also a bully and one of the Crater Worm jocks on the school's crushball team.
• Marcus Xenon is another one of Rodney's friends who is also a bully. Marcus, like Eileen, is a green, three-eyed, octopus-like alien, only without hair and having a more frequent tendency to moving bipedal.
• Violet (voiced by Ashley Johnson) is a girl who is friends with Brittany and Megan. Violet tends to be much more shy than the other girls of her class and she even reveals in the season 2 finale that she has a crush on Lloyd, though this was never mentioned again afterwards. According to this same episode, she is president of the school yearbook staff.

Note: All episodes in this season aired on ABC.

Note: All episodes in this season aired on ABC, unless noted.