Matthew "Matt" McGuire is Lizzie's younger brother. He is portrayed as a scheming, witty, cheeky young prankster who goes to extreme lengths to continuously annoy and irritate his older sister Lizzie, and sometimes his mom and dad. At school, he is known to be the stereotype of the class clown. He is shown to be lazy, and, although he does have many potential talents, he doesn't use them much. He has a best friend named Lanny Onasis, who did not speak on-screen, but Matt was able to understand him anyway. Matt was also sometimes menaced by a bully named Haywood Biggs. Matt is clever, wily and has a reputation for getting into trouble. Matt and Lizzie shared a typical brother-sister relationship. They fooled around and annoyed each other, but were always there for each other at the end of each episode. Matt is also rather intelligent and creative, and knows how to humor people.
- Matt started kindergarden in 1996.
- Matt once got his head stuck in the banister, and Gordo helped free him.
- In the episode "Election", Matt pretends to have an imaginary friend, Jasper, to get attention and gifts from his parents.
- In the episode "Facts of Life" Matt and Lanny form a rock band, with Rick Marotta as drummer, but get tired of it after one backyard concert.