- Patton Oswalt - Wonderboy (voice)
- H. Jon Benjamin - The Master (voice)
- Nathan Fillion - Brown Widow (voice)
- Stephen Colbert - Professor Impossible (voice)
- Seth Green - Lance Hale / Mrs. Z (voice)
- Steve Park - Mike Sorayama (voice)
- John Hodgman - Dale Hale (voice)
- Dana Snyder - The Alchemist (voice)
- Dana Snyder - President Breyer (voice)
- Gillian Jacobs - Marsha Backwood (voice)
- Kevin Conroy - Captain Sunshine (voice)
- Charles Parnell - Mandalay (voice)
- Charles Parnell - Jefferson Twilight (voice)
- Brendon Small - Action Johnny (voice)
- Brendon Small - Surgeon / OSI Scientist / SPHINX Agent 1 (voice)
- Brendon Small - Jonny Quest (voice)
- Brendon Small - Sgt. Hatred (voice)
- Brendon Small - Agent Hauser (voice)
- Brendon Small - Swifty / Hector / Crime-o-dile Henchman / White Noise (voice)
- Brendon Small - Resistance 1 (voice)
- Brendon Small - Plastic Surgeon (voice)
- Paul Boocock - Dr. Jonas Venture (voice)
- Paul Boocock - Dr. Jonas Venture / Additional Voices (voice)
- Paul Boocock - Jonas Venture Sr. / Sandow / Samuel Clemens (voice)
- Paul Boocock - Dr. Jonas Venture / More Pirates (voice)
- Paul Boocock - Sonny / Interpreter / Little Jorgé (voice)
- Paul Boocock - Dr. Jonas Venture / OCLF Leader (voice)
- Paul Boocock - Jonas Venture Sr. / Additional Voices (voice)
- Paul Boocock - Fighter Pilot / O.S.I. Instructor (voice)
- Paul Boocock - Tigerriffic / Therapist / Prison Guard 2 (voice)
- Paul Boocock - Priest 1 / Jonas Venture (voice)
- Paul Boocock - Highway Cop / Scared Straight Kid 1 (voice)
- Bill Hader - Professor Impossible / Phage (voice)
- Bill Hader - Professor Impossible (voice)
- Bill Hader - Professor Impossible / Alien villain (voice)
- Toby Huss - General Treister (voice)
- Toby Huss - Scaramantula (voice)
- Steven Rattazzi - Dr. Orpheus (voice)
- Lisa Hammer - Triana Orpheus (voice)
- Lisa Hammer - Jeanie / Leslie Cohen / Lesliebots (voice)
- Lisa Hammer - Jeanie (Mrs. Tom) (voice)
- Lisa Hammer - Princess Tinglepants (voice)
- Cristin Milioti - Sirena (voice)
- Cristin Milioti - Receptionist
- Cristin Milioti - Mrs. Wandering Spider (voice)
- Cristin Milioti - Stab Girl (voice)
- Cristin Milioti - Night Nurse Cindy Marie Abrams (voice)
- Cristin Milioti - Kate (voice)
- Cristin Milioti - Madison (voice)
- Cristin Milioti - Nurse (voice)
- Cristin Milioti - Mrs. Fitzcarraldo (voice)
- Cristin Milioti - Novia
- Cristin Milioti - Millinery Ghosts (voice)
- Keith Crofford
- J.G. Thirlwell
Steve Park interpreta a Mike Sorayama (voice) en la serie.
Doc Hammer hace el papel de Dr. Girlfriend / Henchman 21 (voice).
Patrick Warburton interpreta a Brock Samson (voice) en la serie.
James Urbaniak interpreta a Dr. Venture (voice) en la serie.
Michael Sinterniklaas hace el papel de Dean Venture (voice).
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