This episode was used by Elaine E Sutherland, who is a member of the Law Society of Scotland's Family Law Sub-Committee and Professor of Child and Family Law at the Law School, Stirling University, to describe the potential problems of letting one kid babysit the others. While one child may be a capable babysitter, it is not guaranteed that the other kids accept the babysitters authority.
It is revealed that Bart is 2 years and 38 days older than Lisa.
Malaria Zone is one of the stores featured at the Springfield Squidport. The store is a parody of the Banana Republic clothing store, which was originally known for its catalogue of safari-themed retail locations. The brand would be purchased by The Gap in 1983, who rebranded Banana Republic as a luxury clothing line. The store's safari theme would be abandoned altogether upon the takeover.
On the waterfront, Rainier Wolfcastle opens a restaurant called "Planet Hype". This is a parody of the international theme restaurant franchise Planet Hollywood. Wolfcastle is a parody of Arnold Schwarzenegger, who launched Planet Hollywood along with Sylvester Stallone, Bruce Willis, Demi Moore and Whoopi Goldberg in 1991. According to Matt Groening, the show had written an entire episode around Planet Hollywood, which featured the voices of Schwarzenegger, Stallone, and Willis as The Three Stooges type of characters. The episode was never animated, because it turned out that it was only the publicist of Planet Hollywood's idea and the actors did not want to participate.
Like numerous preceding episodes, "My Sister, My Sitter" deals with the relationship between Bart and Lisa. Dan Greaney specializes in writing Bart and Lisa episodes from the perspective of a kid.