
•Helga Phugly (Lea DeLaria) – A fat, toad-like girl who will eat virtually anything. She lives in a fantasy world, believing that she is pretty and popular and that the "Debbies'" actually like her (she seems to stubbornly believe this, as when told that the Debbies hate her, she covered her ears, shut her eyes, and started stomping around humming very loudly). At times, she seems to have a crush on Milo, leading to her kidnapping him in one episode. When her parents went on vacation and never returned, Helga was forced to live at home by herself, eating only rejected wedding cakes from a nearby wedding cake factory and the occasional animal that she spotted. Milo eventually locates her parents when Mrs. Hubbard, a Bible-thumping, gun-toting old woman, tries to adopt Helga. Her last name, Phugly, is derived from the word "fugly", which is a term short for "f***ing ugly".
•Creepy Susie (Jeannie Elias) – A girl who speaks with a deadpan French accent and appears to float instead of walk, as her legs are never shown. She is obsessed with death, and has a problem with pyromania, but it has been revealed she does enjoy hula hoops (even though her stiff movements make it physically impossible for her to use one). Susie seems to get along well with Mikey, (and sometimes Helga.) appearing in many scenes alongside him.
•Peggy (Becky Thyre) – A one-breasted girl who lacks a lower jaw, causing her to spit and talk with a lisp. Despite her deformities, Peggy is incredibly cheerful and upbeat. The daughter of a gay couple, she dreams of being president and marrying a handsome speech therapist.
•Mikey (Jeannie Elias) – A boy saddled with a dangling, doubled posterior. Standard underwear will not fit him, so he wears his grandmother's old bra like backwards suspenders. He is also known to habitually probe his nose and ears with his finger. Because of his larger deformed posterior, he takes jokes about the area more literally especially since they often come true soon after. As a running gag, he is inflicted with severe misfortune in almost every appearance, ranging from being stung by bees to attacked by dogs.