On an ordinary day at Springfield Elementary, Lisa attempts to make friends with a new girl, Francine (who is much larger and tougher than Lisa), but Francine beats up Lisa severely. Even attempting to share an interest in Malibu Stacy does not work since the doll that Francine has turns out to be Lisa's, which she then ruins. Lisa attempts to hire the school bullies (Nelson, Dolph, Jimbo, and Kearney) to protect her, but they refuse since girls fight dirtier than boys (and boys tend to be more vulnerable to falling in love). It is up to Lisa to investigate by herself the reason why Francine is targeting her.
Meanwhile, Homer starts to fear that Maggie could die from touching things unsafe to her when he hears this from a childproofing saleswoman. As a result, he starts his own childproofing crusade, selling cheap but safe and effective products and making Springfield safe for children. However, this causes the baby-injury-related business in Springfield to go in decline. Homer feels bad for making people such as pediatricians lose their jobs and thus he ends his childproofing career.
Lisa does scientific research on nerds and discovers that the odor of the chemical nerd pheromone "poindextrose" attracts bullies like Francine, proving that both nerds and bullies are predisposed to be what they are. Lisa then tests the poindextrose extracted from the nerds on famous boxer Drederick Tatum by putting it on his clothes when he visits the school. This causes Nelson to start punching Tatum uncontrollably and give him a wedgie. Lisa demonstrates her experiment at Professor Frink's science conference, the "12th Annual Big Science Thing", using an antidote on herself and making Francine peaceful and friendly towards her, the antidote being just salad dressing which covers up the smell of the poindextrose. The audience is impressed and Lisa is awarded a gift certificate from J. C. Penney for her research. However, the salad dressing soon runs out and Francine goes on a rampage beating up all the scientists in the room.