Harriet is an 11-year-old girl living a privileged life on the Upper East Side of Manhattan. She wears old jeans and a tool belt equipped for her primary hobby: spying on her neighbors and classmates. Aspiring to be a professional spy and a writer, she meticulously records her blunt observations about the people around her in a secret notebook. She relies heavily on fixed daily routines, such as eating a tomato and mayonnaise sandwich for lunch, to feel secure in her environment.

Ole Golly is a dark-haired woman in her 30s who serves as Harriet's live-in nanny and primary authority figure. She is highly practical, well-read, and frequently quotes classic literature to teach Harriet life lessons. Recognizing Harriet's intense curiosity, she encourages the girl to observe the world but warns her that observation must eventually be paired with compassion and understanding.

Sport is an 11-year-old boy and one of Harriet's closest confidants. Because his father is an impractical writer, Sport assumes the heavy burden of managing his household's cooking, cleaning, and financial ledgers. He hopes to become a professional baseball player but mathematically calculates that becoming a certified public accountant is a safer backup plan.

Janie is an 11-year-old girl and Harriet's other best friend. Operating a chemistry set in her bedroom, she functions as a junior scientist who conducts volatile experiments and casually threatens to blow up the world. She fiercely resists traditional expectations, flatly refusing her mother's demands that she attend dancing school to become a proper lady.

Mrs. Welsch is Harriet's attractive, affluent mother. Operating as an Upper East Side socialite, she spends her afternoons playing bridge and her evenings at parties. She trusts her hired staff entirely with Harriet's daily upbringing, focusing instead on broader social expectations for her daughter.

Mr. Welsch is a successful television executive whose career occupies the vast majority of his time. Like his wife, he relies heavily on the household staff to manage his domestic life and raise his daughter. He is genuinely fond of Harriet but remains frequently distracted by professional pressures.

Waldenstein is a heavy-set, cheerful man with darkish skin who works using a delivery bicycle. He pursues a romance with Ole Golly, bringing a sense of warmth and spontaneity that disrupts the strict routines Harriet is accustomed to.

Mrs. Golly Senior is Ole Golly's mother, described as a large woman wearing an enormous sweater. She has lived her entire life in a single room, possessing absolutely no intellectual curiosity or interest in the outside world.

Sport's father is an eccentric and highly impractical writer. Utterly lacking a head for business or daily chores, he forces his young son to assume all domestic responsibilities, from paying bills to cooking meals.

Janie's mother is a traditional parent who grows increasingly frustrated by her daughter's dangerous scientific hobbies. She attempts to enforce conventional gender roles by threatening to send Janie to dance classes.

Mrs. Plumber is a wealthy woman living on Harriet's spy route. She spends her days entirely in bed, viewing her bedridden state and constant telephone conversations as a grand career.

Harrison Withers is a solitary craftsman who makes birdcages for a living. He shares his apartment with 26 cats, enjoying a simple existence where he eats yogurt while feeding kidneys to his numerous pets.

Little Joe Curry is the delivery boy for the Dei Santi family grocery store. He constantly snacks on the store's merchandise while secretly slipping food to hungry neighborhood children.

Mrs. Dei Santi co-owns and operates the local grocery store. She is highly expressive and emotional, frequently experiencing dramatic reactions regarding her children's behavior and the daily operations of the business.

Fabio is the son of the local grocery store owners. He actively avoids helping with the family business, preferring to borrow the delivery truck to pursue outside work as a salesman.

The Robinsons are a wealthy, idle couple who live on Harriet's spy route. They spend their time acquiring bizarre and massive art objects simply to invite guests over to view their purchases.

The Welsch family's cook prepares the daily meals and maintains the kitchen. She accommodates Harriet's rigidly fixed eating habits, though the child's exact demands occasionally try her patience.

Dr. Wagner is a very tall psychologist with bright red hair standing up behind a bald crown. He wears thick glasses and evaluates his young patients by engaging them in board games while taking careful notes.