The episode title is a play on "Mother's Little Helper", a song by The Rolling Stones, which in turn is a euphemism for certain prescription drugs believed to be commonly used (or abused) by middle-class women in the US and UK in the 1960s (such as barbiturate sleeping pills, amphetamine diet pills, and benzodiazepine tranquilizers).
Bart is shown reading a book called 'The 7 Habits of Highly Effective Pre-Teens' and gives a copy of 'Chicken Soup for the Loser' to Homer. These are plays on the real books 'The 7 Habits of Highly Effective People' and 'Chicken Soup for the Soul' (both of which produced multiple sequels and spin-offs).
Homer says that Bart "has gone from Goofus to Gallant", a reference to the comic strip "Goofus and Gallant", which appeared in 'Highlights', a magazine for children. Typically, Goofus would do something rude or destructive, while Gallant served as an example of proper behavior.
The drug company that produces the fictitious drug Focasyn is called "The Pharm Team", a pun on "farm team", a team used to groom players for a professional sports team. For example, baseball in the United States has an extensive farm team system.