The title references the film The Hand That Rocks the Cradle.
The ending with Stewie's were-wolf yellow eyes and maniacal laughter is taken from Michael Jackson's "Thriller" video.
Bonnie's revealing that the voicework is done to support her gambling addiction is a reference to Jennifer Tilly, her voice actress, who is also a professional poker player.
The evil Stewie plot parallels the Star Trek episode "The Enemy Within", in which a transporter accident splits Captain Kirk into a docile version and an evil version that appears when the crew leaves the transporter room. The docile Captain Kirk's weak will is mimicked when Stewie makes a poor attempt to insult Brian and ends up agreeing with him. The music playing when evil Stewie appears is also from "The Enemy Within".
When dropping Meg off at the school, Joe asks about Lady Gaga. Later, when still in the car he makes a reference to her song "Born This Way".
Stewie mentions Brian "going all Michael Hutchence" when he finds him being strangled with his collar. This is a reference to Hutchence's death, in which he hung himself with his belt.