The show frequently features discussions and monologues that express skepticism and sometimes mockery towards certain LGBTQ+ identities and advocacy efforts, particularly concerning transgender issues. While diverse viewpoints may occasionally be presented, the host's consistent framing often contributes to a problematic portrayal, endorsing ridicule rather than affirmation.

Real Time with Bill Maher frequently discusses transgender themes, often presenting them through a lens of skepticism and criticism. The show's host and guests often question the validity of trans identities and frame related issues as problematic societal trends, leading to a portrayal that is largely dismissive or mocking rather than affirming.

The show consistently critiques Christianity, particularly its fundamentalist interpretations and political influence, portraying it as irrational, hypocritical, and often harmful through satire and direct argumentation.

The show's narrative, heavily influenced by Bill Maher, consistently portrays Islam as a problematic and often oppressive religion, particularly in its more fundamentalist interpretations, highlighting issues like extremism and women's rights.

Judaism is frequently subjected to critique, especially concerning its dogmatic aspects and the actions of religious fundamentalists, presenting it as problematic and contributing to societal issues.