Debi Derryberry as Jimmy Neutron / Alien Actress / Alien Woman (voice)

Rob Paulsen as Carl Wheezer/Mr. Wheezer/Mrs. Wheezer/Test Pilot/Announcer (voice)

Jeffrey Garcia as Sheen Estevez / Army Guard (voice)

Frank Welker as Goddard (voice)

Carolyn Lawrence as Cindy Vortex (voice)

Crystal Scales as Libby Folfax (voice)

Tim Allen as Meldar Prime (voice)

Alyssa Milano as April (voice)

Carlos Alazraqui as Sr. Estevez (voice)

Jeff Bennett as Gorlock #2 / Brain #1 (voice)

Megan Cavanagh as Judy Neutron / Mrs. Vortex (voice)

Jim Cummings as Brain #2 / Mayor Quadar (voice)

Mark DeCarlo as Hugh Neutron / Emergency System / Gen. Abercrombie (voice)

Jess Harnell as Meldar Prime (singing voice)

Joe Lala as Sr. Estevez (voice)

Phil LaMarr as Bolbi Stroganofsky / British Tourist (voice)

Billy West as Sam / Corky Shumatsu (voice)

Grey DeLisle as Vendanna (voice)