Mrs. Piggle-Wiggle is a kind, enigmatic woman who lives in a whimsical upside-down house and smells comfortingly of sugar cookies. She claims to be the widow of a pirate who buried treasure in her backyard before he died. She loves the neighborhood children, treating them with respect and viewing their misbehaviors as curable ailments rather than character flaws. She regularly helps frustrated parents by inventing clever, natural-consequence cures for their children's habits.

Hubert is a generally generous boy suffering from "Won't-Pick-Up-Toys-itis." He receives lavish gifts from his grandfather but enjoys building simple toys out of orange crates just as much. His refusal to clean his room eventually leads to him becoming trapped by his own mess.

Mary is a clever girl with beautiful red hair and brown eyes. She develops "Answer-Backer" symptoms, taking pride in making rude, witty remarks whenever adults ask her to do things. She learns empathy when forced to spend time with a parrot who mirrors her bad attitude.

Dick is a smart, usually polite, and obedient boy who develops a severe case of selfishness. He cares more about keeping his possessions to himself than about having friends. He realizes the value of sharing only after his parents label all his belongings with "DON'T TOUCH" signs, causing his peers to avoid him.

Patsy is typically a sweet and compliant girl who suddenly develops a fierce aversion to bathing. She avoids washing for weeks until a thick layer of dirt accumulates on her skin. She only changes her mind when she wakes up to find radishes sprouting from her dirty arms and head.

Bobby, Larry, and Susan are siblings who suffer from the "Never-Want-To-Go-To-Bedders" ailment. They enjoy playing board games together, with Larry often acting as the ringleader who encourages the others to stay awake. Their refusal to sleep eventually leaves them too exhausted to enjoy birthday parties and movies.

Allen is a sturdy boy with curly brown hair who develops a habit of eating minuscule portions of food extremely slowly. He finds amusement in his tiny meals until the lack of nutrition leaves him weak. He corrects his behavior when he realizes he lacks the energy to ride his favorite pony.

Anne and Joan are pretty twin sisters afflicted with "Fighter-Quarreleritis." Joan tends to act as the instigator, while Anne is more sensitive and gullible. Their constant bickering heavily disrupts their household until they are forced to witness how unpleasant their behavior sounds to others.

Mary Lou is an eight-year-old girl who intensely dislikes washing dishes. She is the first child Mrs. Piggle-Wiggle invites into her upside-down house. Her willingness to turn a dreaded chore into an imaginative game sparks a long-standing friendship between Mrs. Piggle-Wiggle and the rest of the neighborhood children.

Kitty is a neighborhood girl who hates making beds. She learns to enjoy the household chore when Mrs. Piggle-Wiggle turns it into a high-stakes game involving a Cruel Queen searching for wrinkles in the sheets.

Mrs. Prentiss is Hubert's mother. She spends an inordinate amount of time picking up after her son until she reaches a breaking point. She seeks advice from neighbors before finally relying on Mrs. Piggle-Wiggle's wisdom to teach Hubert a lesson.

Mrs. O'Toole is Mary's mother. She struggles to correct her daughter's sudden habit of answering back. She follows Mrs. Piggle-Wiggle's advice by bringing a rude parrot into the home to mirror her daughter's behavior.

Mrs. Thompson is Dick's mother. She implements the "Selfishness Kit" cure by painstakingly labeling and padlocking all of her son's possessions, demonstrating a strong commitment to correcting his greedy behavior.

Mr. Thompson is Dick's father. He initially suggests corporal punishment before recommending they call Mrs. Piggle-Wiggle instead. He displays a somewhat detached attitude toward daily child-rearing, preferring to read the evening paper.

Patsy's mother seeks community advice before turning to Mrs. Piggle-Wiggle. She patiently follows the unconventional "Radish Cure," allowing her daughter to collect layers of dirt over several weeks until seeds can finally be planted on her skin.

Patsy's father assists his wife in executing the "Radish Cure." He humorously notes how repulsive his daughter looks while she is covered in thick layers of topsoil.

Mrs. Gray is the mother of Bobby, Larry, and Susan. Exhausted by their bedtime whining, she tentatively agrees to Mrs. Piggle-Wiggle's suggestion to let them stay up as late as they want, stepping back to let natural consequences take over.

Mr. Gray is the father of Bobby, Larry, and Susan. He participates in the natural-consequences cure by going to sleep on his own schedule and leaving the children to manage their own late-night hours.

Allen's mother becomes highly concerned when he begins eating minuscule bites of food. She diligently serves his meals on increasingly tiny dishes provided by Mrs. Piggle-Wiggle until he finally realizes the physical cost of his habits.

Mrs. Russell is the mother of Anne and Joan. Deeply stressed by her daughters' constant fighting, she participates in the "Fighter-Quarrelers Cure" by aggressively mimicking their trivial arguments alongside her husband.

Mr. Russell is the father of Anne and Joan. He agrees to Mrs. Piggle-Wiggle's cure, spending an entire day artificially quarreling with his wife to show his daughters exactly how unpleasant their behavior is.

Penelope is Mrs. Piggle-Wiggle's parrot. She speaks exclusively to children and acts as a living archive of rude phrases. She cures Mary O'Toole by being exceptionally annoying and preemptively shouting rude remarks before Mary can say them.

Wag is Mrs. Piggle-Wiggle's pet dog. He is highly friendly with the neighborhood children, who are always eager to adopt his puppies when he has litters.

Lightfoot is Mrs. Piggle-Wiggle's pet cat. She is exceptionally calm and allows visiting children to incorporate her into their games, even letting them curl her tail neatly while they clean.

Spotty is Mrs. Piggle-Wiggle's pony. Riding Spotty is a highly coveted activity among the neighborhood children, and the physical demands of riding him provide the exact motivation Allen needs to resume eating a normal diet.