Maguire married his long-time relationship partner, jewelry designer Jennifer Meyer, on September 3, 2007, in Kona, Hawaii. The couple first met in 2003 while Maguire was shooting the movie Seabiscuit at Universal Studios and became engaged in April 2006. They have a daughter named Ruby Sweetheart Maguire (born November 10, 2006). Ruby's middle name comes from a childhood nickname of Meyer's given to her by her grandmother, who died a few months before Ruby's birth.

Maguire has been a vegetarian for over 14 years and is working toward a vegan diet, though he makes vegetarian changes in his diet to either gain or lose weight for movie roles, like dramatically decreasing his calorie intake for Seabiscuit followed by a rapid increase to regain the weight for Spider-Man 2. On the subject of vegetarianism, Maguire notes that "I’m close to being a vegan, but I’m not one, technically. I don’t eat eggs, or nearly any dairy--no cheese or milk. I do eat honey, and a piece of milk