"Mary Hartman, Mary Hartman" features LGBTQ+ characters, notably Pat Gimble, a dignified gay friend, and Charlie Haggers, whose affair with a man is part of the show's satirical narrative. The series integrates these identities into its complex portrayal of human foibles without resorting to mockery or degradation, offering a progressive and largely affirming depiction for its time.

Mary Hartman, Mary Hartman featured a prominent storyline involving Charlie Haggers' transsexual identity and desire to transition. The show explored the resulting marital and societal challenges through its signature satirical lens, often critiquing societal reactions. The portrayal was complex, neither explicitly affirming nor overtly denigrating trans identity, reflecting a neutral exploration for its time.

The show consistently satirizes the hypocrisy, superficiality, and often absurd manifestations of Christianity among its characters and institutions. The narrative frequently exposes the disconnect between professed faith and actual behavior, portraying religious adherence as often performative, misguided, or a source of delusion within the show's cynical view of suburban life.