South Park frequently uses satire to critique homophobia and transphobia, often portraying LGBTQ+ characters with dignity despite its crude humor. While it employs offensive language and stereotypes for comedic effect, the narrative consistently targets bigotry, ultimately affirming LGBTQ+ identities and relationships.

The portrayal of transsexual themes in South Park, primarily through Mr. Garrison's arc, is complex and satirical. While offering an absurd exploration of gender identity, the show frequently employs shock humor and mockery, presenting transition as a source of personal dysfunction and public spectacle rather than with consistent dignity or empathy.

The show consistently satirizes the hypocrisy, fundamentalism, and institutional flaws within Christianity, often portraying its adherents and practices as foolish or misguided.

The show's narrative condemns violent extremism and champions free speech in the face of threats, rather than critiquing the religion of Islam itself. It positions the audience against those who use violence to enforce religious dogma.

Despite satirizing Jewish culture and stereotypes, the narrative consistently condemns antisemitism (primarily through Cartman's bigotry) and often positions Jewish characters like Kyle as sympathetic and moral.