| Elizabeth Daily | | Tommy Pickles (voice) |
| Christine Cavanaugh | | Chuckie Finster (voice) |
| Kath Soucie | | Philip Deville / Lillian Deville / Betty Deville (voice) |
| Melanie Chartoff | | Didi Pickles / Minka (voice) |
| Phil Proctor | | Howard DeVille / Igor (voice) |
| Cree Summer | | Susie Carmichael (voice) |
| Mary Gross | | Woman Guest (voice) |
| Kevin McBride | | Male Guest (voice) |
| Andrea Martin | | Aunt Miriam (voice) |
| Michael Bell | | Ch |
| Tress MacNeille | | Charlotte Pickles (voice) |
| Jack Riley | | Stu Pickles (voice) |
| Busta Rhymes | | Reptar Wagon (voice) |
| Joe Alaskey | | Grandpa Lou Pickles (voice) |
| Cheryl Chase | | Angelica Pickles (voice) |
| Tony Jay | | Dr. Lipschitz (voice) |
| Edie McClurg | | Nurse (voice) |
| Hattie Winston | | Dr. Lucy Carmichael (voice) |
| Laurie Anderson | | Newborn Baby (singing voice) |
| Beck | | Newborn Baby (singing voice) |
| B-Real | | Newborn Baby (singing voice) |
| Jakob Dylan | | Newborn Baby (singing voice) |
| Gordon Gano | | Newborn Baby (singing voice) |
| Lenny Kravitz | | Newborn Baby (singing voice) |
| Lisa Loeb | | Newborn Baby (singing voice) |
| Iggy Pop | | Newborn Baby (singing voice) |
| Phife Dawg | | Newborn Baby (singing voice) |
| Lou Rawls | | Newborn Baby (singing voice) |
| Dawn Robinson | | Newborn Baby (singing voice) |
| Patti Smith | | Newborn Baby (singing voice) |
| Fred Schneider | | Newborn Baby (singing voice) |
| Kate Pierson | | Newborn Baby (singing voice) |
| Cindy Wilson | | Newborn Baby (singing voice) |
| Tara Strong | | Dylan Pickles (voice) |
| Gregg Berger | | Circus TV Announcer (voice) |
| Abraham Benrubi | | Serge (voice) |
| Charlie Adler | | United Express Driver (voice) |
| Roger Clinton | | Air Crewman (voice) |
| Margaret Cho | | Lt. Klavin (voice) |
| Steven Zirnkilton | | Reporter (voice) |