The Simpsons (1989) creative staff told Seth MacFarlane and his writers they had free rein to do anything they wanted with the characters and not to pull any punches. This was partly because creative staff did not consider "The Simpsons Guy" a crossover, but an episode fully set in Family Guy's universe, and therefore not subject to issues of continuity or canon.
In the back row of the courtroom scene you can see Matt Groening and Seth MacFarlane. MacFarlane is in the first seat on the right, and Groening is in the leftmost seat on the left side.
During the last scene of the episode, Stewie says Bart sounds like a girl. Bart's voice is supplied by Nancy Cartwright.
Roger from American Dad! (2005) makes an appearance on Kang and Kodos' ship during Peter and Homer's fight. As he gets sucked out of the ship, he says "Thanks for having me!". American Dad! (2005) aired its final episode on FOX the previous week.
In the preview for the episode, Stewie says to Moe, "Your sister is getting raped." This resulted in protests to have Seth MacFarlane remove the scene from the episode, which he didn't, which is ironic as protesting by feminists is the scenario that gets the plot of the episode moving.