 | Megan Cavanagh | | Mom / VOX (voice) |
| Mark DeCarlo | | Dad / Pilot / Arena Guard (voice) |
| Debi Derryberry | | James 'Jimmy' Isaac Neutron (voice) |
| Jeffrey Garcia | | Sheen (voice) |
| Bob Goen | | Newscaster (voice) |
| Mary Hart | | Newscaster (voice) |
| Carolyn Lawrence | | Cindy Vortex (voice) |
| Andrea Martin | | Miss Fowl (voice) |
| Candi Milo | | Nick / Britanny / PJ (voice) |
| Rob Paulsen | | Carl / Carl's Mom and Dad / Kid in Classroom / Kid (voice) |
| Crystal Scales | | Libby (voice) |
| Martin Short | | Ooblar (voice) |
| Patrick Stewart | | King Goobot (voice) |
| Jim Cummings | | Ultra Lord / Mission Control / General (voice) |
| David L. Lander | | Yokian Guard / Gus (voice) |
| Kimberly Brooks | | Zachery / Reporter / Angie (voice) |
| Paul Greenberg | | Guard (voice) |
| Laraine Newman | | Hostess (voice) |
| Jeannie Elias | | Little Girl / Camera Person (voice) |
| Michael Hagiwara | | Chris (voice) |
| John A. Davis | | Octapuke Kid / Guard / Bennie (voice) |
| Keith Alcorn | | Bobby / Kid / Control Yokian (voice) |
| Richard Allen | | Digital Voice (voice) |
| Brian Capshaw | | Screamer (voice) |
| Cheryl Ray | | Screamer (voice) |
| Mark Menza | | Yokian Incubator Operator (voice) |
| Frank Welker | | Goddard / Orthgot / Worm / Demon / Poultra / Girl Eating Plant / Oyster (voice) |
| Billy West | | Yokian Officer / Jailbreak Cop / Guard / Robobarber / Anchor Boy / Old Man Johnson / Flurp Announcer / Bobby's Twin Brother / Butch (voice) |
| Matthew Russell | | Hyperactive Kid / Arena Yokian (voice) |
| Carlos Alazraqui | | Sheen's Dad (voice) |
| Dee Bradley Baker | | Norad Officer (voice) |
