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- The title is a spoof of the 2005 film Mr. & Mrs. Smith.
- The Top Gun cutaway parodies Tom Cruise's association with the Church of Scientology.
- Peter refers to the twin beds as "Lucy and Ricky beds", a reference to the characters on I Love Lucy having separate beds.
- As Penelope extracts a vow from Stewie to kill Brian, a soap-opera style advertisement voice over for AXE body spray plays.
- During the fight scene between Stewie and Penelope, the latter used a knife blade hidden within her shoe, a reference to the 1963 James Bond film From Russia with Love.
- The delivery driver collapsing after being shot in the back with several poison darts is similar to the death of Barranca at the hands of the Hovitos in Raiders of the Lost Ark.