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Pepper Ann Pearson
- Voiced by: Kathleen Wilhoite
- Brilliant, but Lazy: She wants to be a scientist, and when she puts her mind to it she's quite intelligent.
- Cloud Cuckoolander: At least that's what most characters think of her, including the twins.
- Fiery Redhead: She even had the nickname "Flare" in one episode!
- Informed Judaism: She's Jewish on her mother's side, but doesn't really seem to practice the religion actively outside of a few holidays with the family.
- Meganekko: She's got glasses, all right!
- Mixed Ancestry: Pepper Ann is Jewish on her mom's side of the family and Spanish, British, and Navajo Indian on her dad's side (though her dad sounds like he could also be Australian).
- Miss Imagination: There are almost Family Guy-like cuts to how she sees or imagines things.
- Passionate Sports Girl: She's into sports, all right, and she's passionate.
- Talking To Them Self: She frequently has discussions with her conscience in any reflective surface, or any place where she can see her own face—even in a bowl of pasta!
- Tomboyish Ponytail: She's a tomboy, all right, and she's got a ponytail.
- Unwanted Assistance: In universe. As a Running Gag, Pepper Ann is chronically bad at helping people and giving advice. Lampshaded in "The Amazing Becky Little."Milo: "How to put this... hmm... often-times when to attempt to help people they end up worse off than before you-"Pepper Ann: "Don't you think I know that?"
- Voiced by: Clea Lewis
- Beware the Nice Ones: She's cute and speaks softly, but she's proven able to hypnotize her own teacher, Jedi-style!
- Catchphrase: Nicky has "absolutamente." Though she doesn't say it quite as constantly as the regular catchphrase it does pop up from time to time.
- Mood-Swinger: She's proven capable of changing to very strong anger when the situation calls for it.
- Only Sane Man: When she is not having her random outbursts, Nicky is close to being the only Normal person in Hazelenut.
- Peek-a-Bangs: Her long hair goes with her soft-spoken and bookish personality.
- Sibling Rivalry: With Becky.
- Silk Hiding Steel: Demure as she looks, never underestimate her.
- The Smart Guy: She's very book-smart.
- Why Did It Have to Be Snakes?: The very same episode dealt with PA trying to help Nicki figure out why she was so afraid of swans. It led to PA realizing that her fear probably stemmed from her feelings of resentment towards her older sister Becky in a sort of The Ugly Duckling transference. Nicki conceded that actually made sense. Subverted, though, when Becky states she's afraid of swans too, and the reason appeared to be due to a frightening swan toy they used to have.
- Voiced by: Danny Cooksey
- Ambiguously Brown: But canonically of Hawaiian descent.
- Cloud Cuckoo Lander: He doesn't seem to always be on the same wavelength as everyone else.
- The Muse: One episode shows him talking to one, similar to Pepper Ann talking to her reflection.
- Nice Guy: Milo is all around decent and friendly person.
- Nice Hat: Part of his everyday wardrobe is his hat.
- Token Minority: In a main-character cast of Two Girls and a Guy, both girls are white, and he's dark-skinned.
- You Gotta Have Blue Hair: Although when it's lampshaded, he insists that it's actually black.
Margaret Rose "Moose" Pearson
- Voiced by: Pamela Segall
- Deadpan Snarker: Fitting with her stoic personality, the delivery of her funny lines is consistently deadpan.
- One of the Boys: She's even more tomboyish than Pepper Ann!
- Only Known by Their Nickname: Her real name is Margaret Rose, but no one ever uses it.
- Only Sane Woman: At times.
- Samus Is a Girl: She can be mistaken for a boy pretty easily.
- The Stoic: She doesn't show much emotion on the series.
- Vocal Dissonance: Sounds like a teenage boy (Pamela Segall Adlon voices her in one of the few times she voices a boy who doesn't have that shrill, obnoxious voice like Pajama Sam, Milo Oblong, and Otto Osworth have. It sounds more like Bobby Hill or Clark Petersnote from King of the Hill if it were pitched down)
- Voiced by: Brenda Chapman
- Amazingly Embarrassing Parents: Lydia occasionally slips into this, but especially when she took Pepper Ann bra shopping.
- Amicably Divorced: From her former husband. Lifestyle seems to have been the main reason they split up since his job required him to travel a lot. Whenever the two interact it's clear they still get along fine, even if they do engage in a bit of ribbing.
- Funny Afro: Several flashbacks show Lydia used to have one. Though given her background it's probably better described as a Jewfro.
- Glamorous Single Mother: Averted, and in one episode she has an entire comedy act around how not glamorous it is.
- Generation Xerox: Punishes Pepper Ann for sneaking out to a party, but then Pepper Ann finds Lydia's diary from when she was in middle school and learns that Lydia also sneaked out of the house without her parent's permission.
- Hartman Hips: A rare overweight example.
- Jewish Mother: Subverted. Lydia is Jewish — or at least, celebrates Jewish holidays to keep with tradition, but doesn't act like a stereotypical Jewish mom.
- Mama Bear: Lydia is hinted at having this side to her. One time, she physically threatens a waiter who is making her late for Pepper Ann's play.
- Meganekko: She wears glasses and is a good looking woman
- Voiced by: Susan Tolsky