Debi Derryberry

as James 'Jimmy' Isaac Neutron (voice)

Megan Cavanagh

as Judy Neutron / VOX (voice)

Mark DeCarlo

as Hugh Neutron / Pilot / Arena Guard (voice)

Jeffrey Garcia

as Sheen Estevez (voice)

Patrick Stewart

as King Goobot V (voice)

Martin Short

as Ooblar (voice)

Frank Welker

as Goddard / Poultra (voice)

Rob Paulsen

as Carl Wheezer / Mr. and Mrs. Wheezer / Kid in Classroom (voice)

Carolyn Lawrence

as Cindy Vortex (voice)

Crystal Scales

as Libby Folfax (voice)

Candi Milo

as Nick Dean / Britney / PJ (voice)

David L. Lander

as Yokian Guard / Gus (voice)

Carlos Alazraqui

as Mr. Estevez (voice)

Jim Cummings

as Ultra Lord / Mission Control / General Bob (voice)

Keith Alcorn

as Bobby / Kid / Control Yokian (voice)

Kimberly Brooks

as Zachary / Reporter / Angie / Libby's Mom (voice)

Andrea Martin

as Ms. Winfred Fowl (voice)

Billy West

as 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)

Mary Hart

as Yokian Newscaster #2 (voice)

Bob Goen

as Yokian Newscaster #1 (voice)

Dee Bradley Baker

as Norad Officer (voice)

Laraine Newman

as Hostess (voice)

John A. Davis

as Octapuke Kid / Guard / Bennie (voice)

Paul Greenberg

as Guard (voice)

Mark Menza

as Yokian Incubator Operator (voice)

Jeannie Elias

as Little Girl / Camera Person (voice)

Michael Hagiwara

as Chris (voice)

Richard Allen

as Digital Voice (voice)

Brian Capshaw

as Screamer (voice)

Cheryl Ray

as Screamer (voice)

Matthew Russell

as Hyperactive Kid / Arena Yokian (voice)