It's Always Sunny in Philadelphia offers a complex, satirical portrayal of LGBTQ+ themes. While the main characters frequently exhibit homophobia, the show consistently lampoons their bigotry. Mac's long-running arc, culminating in a surprisingly earnest and affirming coming-out, provides a powerful moment of queer validation, positioning the show's net impact as positive despite its often problematic humor.

It's Always Sunny in Philadelphia features Carmen, a recurring transsexual character. While Carmen herself is not portrayed as a caricature, the show frequently uses the main characters' transphobic language (e.g., "tranny") and prejudiced reactions to her identity as a source of humor. This portrayal, lacking explicit in-narrative critique of the slurs and prejudice, results in a net negative impact.

The show consistently portrays characters who claim Christian faith as hypocritical, judgmental, and morally bankrupt, using religion as a shield for their terrible behavior. Mac's Catholicism is a running gag, highlighting his internal struggles and often absurd interpretations of doctrine without offering counterbalancing positive portrayals.

The show satirizes the gang's ignorance, prejudice, and use of stereotypes regarding Judaism. The humor derives from the characters' bigotry and absurdity, not from a critique of the religion itself, thereby positioning the audience to condemn the characters' views.