Nip/Tuck features several prominent LGBTQ+ characters and themes, exploring various sexualities and identities within its signature dark and sensationalized narrative. While some characters are depicted with dignity, other portrayals can lean into dramatic or problematic tropes. The show's overall approach is more observational and boundary-pushing than explicitly affirming or denigrating, resulting in a largely neutral net impact on LGBTQ+ representation.

Nip/Tuck features Ava Moore, a prominent transsexual character whose identity is initially presented as a shocking secret and a source of betrayal for her love interest, Christian Troy. The narrative uses her trans identity primarily as a dramatic plot device, focusing on the 'deception' trope and Christian's subsequent crisis, rather than affirming trans lives or depicting her identity with consistent dignity.

The show consistently portrays Christian characters and institutions as hypocritical, morally flawed, or judgmental, often linking religious adherence to repression or denial rather than genuine spiritual growth. The narrative frequently exposes the gap between professed faith and actual behavior, offering little counterbalancing positive portrayal.