Greg is a 12-year-old middle schooler who frequently experiences humorous misadventures and tries to avoid trouble. He is highly observant and analytical, yet he struggles with learning from his mistakes and often exhibits poor judgment. As the middle child, he feels squeezed between an older brother who bullies him and a younger brother who receives preferential treatment. He spends his free time playing an internet game called Net Kritterz, where he cares for a virtual chihuahua.

Mom is an involved, hands-on parent who pushes her sons to mature and understand the value of hard work. She frequently attempts to enforce good behavior through holiday traditions and micromanages the household. Despite her focus on teaching responsibility, she occasionally exhibits dishonest behavior of her own, such as forging an author's signature on a graphic novel.

Dad is a somewhat detached father who prefers to stay in the background but frequently voices his disappointment when his sons make mistakes. He values his personal property, specifically his new sports car, and attempts to teach Greg to stand up against bullies. He spends a portion of a major winter storm safely isolated at a hotel near his office.

Rowley is Greg's naive, loyal, and somewhat gullible best friend. He often annoys Greg with his quirky habits, like skipping at recess or saying the letters "L-O-L" out loud instead of laughing. Despite their frequent disagreements and contrasting personalities, Rowley enthusiastically collaborates with Greg on creative projects like building a manual arcade game and publishing a local neighborhood newspaper.

Manny is the Heffley family's youngest son, a toddler who is precocious, mischievous, and heavily coddled by his parents. He consistently gets his way, whether dictating exactly how his hot dog must be prepared or commanding the family's complete attention. His tantrums and secret pranks often cause significant stress for the rest of the household.

Rodrick is Greg's high-school-aged older brother who frequently bullies him. He is notoriously messy and disorganized, often shirking his familial duties to avoid helping around the house. When a basement flood forces him to temporarily move into Greg's room, his chaotic habits create major tension between the brothers.

Dennis is a student identified as the only remaining bully at Greg's middle school. He alters his aggressive behavior and leaves people alone after the school puts up numerous anti-bullying posters in the hallways.

Dean is a middle school student who has a history of receiving poor treatment from Greg. Greg previously ruined a birthday present intended for him by playing with it first, and Dean later receives a hastily procured Secret Santa gift bearing an embarrassing signature.