| • Christopher McCulloch | voiced | Sgt. Hatred / Hunter Gathers / Commander / The Monarch / Henchman 24 / Watch / Tim-Tom Muppet / Councilman 2, 8, 9 / The Sovereign / Dr. Henry Killinger / General Manhowers / Pete White / Additional Voice / Colonel Hunter Gathers / Sgt. Haine / Tim-Tom Moppet / Pirate Captain / Dr. Z / Additional Voices / Col. Gentleman / Dr. Dugong / Brainulo / The Action Man / Ned / Prof. Impossible / Additional Pirates / Henchman 1 / Mr. Doe / Hunter / Kano / Lloyd Venture / Fantomas / Herr Trigger / Le Tueur / Mile High "Sky Pilot" / Mister Doe / Sgt. Collar / Det. Heat / Police Psychiatrist / Doe / Steve Summers / Scorpio / Copter 5 Guy / Sheriff / Tim-Tom / Henchman 86 / Henchman 87 / Dragoon / Intangible Fancy / Sovereign Head / Councilman 9 / Ro-Boy / Torrid / Monstroso / Dr. Schumpmaker / Sky Pilot / King Gorilla / Roy Brisby / Peter White / Zero / Storm Front / Tiger Shark / Ghost Robot / Fat Chance / Cody / Mr. Polygamy / Lyndon Bee / Pete "Thantos" White / Dr. Odinson / Curse / St. Cloud / Cheetah-Man / Boar-Man / Venturestein | 34 Episodes |
| • Doc Hammer | voiced | Dr. Girlfriend / Henchman 21 / Ward / Kevin Moppet / Councilman 1 & 3 / Billy Quizboy / Billy (Whalen) Quizboy / Shore Leave / Sheila / Underground Quizboy 1 / Dr. Mrs. The Monarch / Dermott Fictel / Extra Pirates / Mr. Cardholder / Shore Leave "Holy Diver" / Go-Fish / Cardholder / Desmond / U.S. Steel / Dermott / Kevin / Red Mantle / Councilman 1 / Dermott Ficktel / The Outrider / Speedy / Rod Mantle / Rod Martin / Dermott Fichtel / Billy "Eros" Quizboy / Col. Gentleman / "Viceroy" / Toaster Face | 31 Episodes |
| • Steven Rattazzi | voiced | Dr. Byron Orpheus / Dr. Byron Orpheus, Some Dolphin, Steven Rattazzi / Dr. Orpheus / Alastair Crowley / Fritz | 22 Episodes |
| • Lisa Hammer | voiced | Triana Orpheus / Triana Orpheus, Waitress 1, Waitress 2 / Triana Orpheus, Leslie Cohen, Lesliebots / Jeanie (Mrs. Tom) / Princess Tinglepants | 17 Episodes |
| • Paul Boocock | voiced | Dr. Jonas Venture / Fighter Pilot, O.S.I. Instructor / Tigerriffic, Therapist, Prison Guard 2 / Highway Cop, Scared Straight Kid / Dr. Jonas Venture, Subway Bum, Taxi Driver, Voice of Impossible Computer / Sonny, Interpreter, Little Jorgé / Jonas Venture Sr. / Additional Voices / Dr. Jonas Venture Sr. / More Pirates / Sandow / Samuel Clemens / Psychiatrist / University President / Homeless Vet / Sonnystein / Gill-Man | 15 Episodes |
| • Dana Snyder | voiced | The Alchemist / President Breyer / Dog-Man | 14 Episodes |
| • Mia Barron | voiced | Molotov Cocktease, Island Girl / Sally Impossible, Jonas Jr.'s Ibezan Houseguest / Sally Impossible / Molotov Cocktease, Debbie / Girl Hitler / Molotov Cocktease / Ladyhawk Johnson | 14 Episodes |
| • James Urbaniak | voiced | Phantom Limb / Councilman 7 / Dr. Jonas Venture Jr. / Professor Fantomas / Oscar Wilde / Sovereign / Rusty Venture / The Rusties / Rusty's Women | 13 Episodes |
| • Charles Parnell | voiced | Mister 1 / Mandelay / Jefferson Twilight | 11 Episodes |
| • Nina Hellman | voiced | Kim, Jollyrancher82 / Lt. Anna Baldavitch, Woman on Cell Phone / Tijuana Prostitute / J.J.'s ride to the Marina / Kim / Woman in Court / Prostitute / Lt. Anna Baldavitch, Cassie / Dr. Tara Quymn / Mz. Quymn / Nancy Quymn | 9 Episodes |
| • Brendon Small | voiced | Plastic Surgeon / Johnny Quest / Resistance 1 / Agent Hauser / Sgt. Hatred / Action Johnny / Surgeon / OSI Scientist / SPHINX Agent 1 | 8 Episodes |
| • T. Ryder Smith | voiced | Baron Werner Ünderbheit / Otto Aquarius / Baron Werner Ünderbheit, Soldier 1 / Baron Ünderbheit / Dean Harris | 6 Episodes |
| • Joanna P. Adler | voiced | Mrs. Manstrong / Myra Brandish / Val / Virginia "Ginnie" Dunne / Drew Quymn | 5 Episodes |
| • H. Jon Benjamin | voiced | The Master | 4 Episodes |
| • Toby Huss | voiced | Scaramantula / General Treister | 4 Episodes |
| • Bill Hader | voiced | Professor Impossible / Phage / Alien Villain / Narrator | 4 Episodes |
| • Kate McKinnon | voiced | Nikki Fichtel / Mrs. Fichtel / TBD / Margaret Fictel / Nikki Fictel / Thalia / Mrs. Fictel | 4 Episodes |
| • Michael Sinterniklaas | voiced | Half-Jackel / D-19 / Dermott's Mom | 2 Episodes |
| • Stephen Colbert | voiced | Professor Impossible | 2 Episodes |
| • Richard Liebmann-Smith | voiced | U.N. Science Director / Mexican University Administrator | 2 Episodes |
| • Terrence Fleming | voiced | Col. Bud Manstrong | 2 Episodes |
| • Sue Gilad | voiced | Patty / Princess Tinyfeet | 2 Episodes |
| • Stephen DeStefano | voiced | Dr. Paul Entmann / Dr. Entmann | 2 Episodes |