South Park's portrayal of LGBTQ+ themes, while often controversial and satirical, includes consistently positive and affirming characters like Big Gay Al and the Tweek x Craig relationship. The show frequently uses humor to critique prejudice, ultimately promoting acceptance and tolerance despite its often provocative methods.

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 portrayal of Islam often revolves around controversy, extremism, and the perceived threats or demands for censorship associated with it, rather than offering a nuanced or affirming view of the faith itself.

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.