 | Debi Derryberry als James 'Jimmy' Isaac Neutron (voice) |
 | Megan Cavanagh als Judy Neutron (voice) / VOX (voice) |
 | Mark DeCarlo als Hugh Neutron (voice) |
 | Jeffrey Garcia als Sheen Estevez (voice) |
 | Patrick Stewart als King Goobot V (voice) |
 | Martin Short als Ooblar (voice) |
 | Frank Welker als Goddard (voice) / Poultra (voice) |
 | Rob Paulsen als Carl Wheezer (voice) / Mr. Wheezer (voice) / Mrs. Wheezer (voice) / Kid in Classroom (voice) |
 | Carolyn Lawrence als Cindy Vortex (voice) |
 | Crystal Scales als Libby Folfax (voice) |
 | Candi Milo als Nick Dean (voice) / Britney (voice) / PJ (voice) |
 | David L. Lander als Yokian Guard (voice) / Gus (voice) |
 | Carlos Alazraqui als Mr. Estevez (voice) |
 | Jim Cummings als Ultra Lord (voice) / Mission Control (voice) / General Bob (voice) |
 | Keith Alcorn als Bobby (voice) / Kid (voice) / Control Yokian (voice) |
 | Kimberly Brooks als Zachary (voice) / Reporter (voice) / Angie (voice) / Libby's Mom (voice) |
 | Andrea Martin als Ms. Winfred Fowl (voice) |
 | Billy West als Bobby's Twin Brother (voice) / Butch (voice) / Jailbreak Cop (voice) / Old Man Johnson (voice) / Robobarber (voice) / Flurp Announcer (voice) / Yokian Officer (voice) / Anchor Boy (voice) / Guard (voice) |
| Bob Goen als Yokian Newscaster #1 |
 | Mary Hart als Yokian Newscaster #2 (voice) |
| Bob Goen als Yokian Newscaster #1 (voice) |
 | Dee Bradley Baker als Norad Officer (voice) |
 | Laraine Newman als Hostess (voice) |
| John A. Davis als Octapuke Kid / Guard / Bennie (voice) |
 | Paul Greenberg als Guard (voice) |
| Mark Menza als Yokian Incubator Operator (voice) |
| John Debney | Original Music Composer |
| Steve Oedekerk | Screenplay |
| Steve Oedekerk | Producer |
| Steve Oedekerk | Story |
| J. David Stem | Screenplay |
| David N. Weiss | Screenplay |
| Gregory Perler | Editor |
| David Grimaldi | Sound Effects Editor |
| Chuck Michael | Sound Effects Editor |
| John A. Davis | Screenplay |
| John A. Davis | Director |
| John A. Davis | Producer |
| John A. Davis | Story |
| Keith Alcorn | Producer |
| Keith Alcorn | Executive Producer |
| Kim Saxon | Production Manager |
| Jon Price | Editor |
| Julia Pistor | Executive Producer |
| Albie Hecht | Producer |
| Steve Kolbe | Director of Photography |
| Chris Sherrod | Director of Photography |
| David E. Fluhr | Sound Re-Recording Mixer |
| Fred Cline | Production Design |
| Ginny McSwain | Casting Director |
| Bob Camp | Storyboard |
| Christopher T. Welch | Supervising Sound Editor |
| Christian P. Minkler | Sound Re-Recording Mixer |
| Paul N.J. Ottosson | Sound Designer |
| Steve Tushar | Sound Effects Editor |
| Brett Paton | Animation |
| Marc Gabbana | Concept Artist |
| Michael Jonascu | Sound Designer |
| James Beihold | Art Direction |
| Tok Braun | Unit Production Manager |
| Paula Kaplan | Casting Director |
