Helluva Boss prominently features multiple LGBTQ+ characters, including central figures Blitzo (bisexual) and Stolas (gay). Their relationships are explored with significant depth, dignity, and complexity, driving core narrative arcs. The show normalizes queer identities and experiences, portraying them as integral to the characters' lives without endorsing ridicule or degradation, resulting in an overall affirming depiction.

Helluva Boss features Sallie May, a trans woman, as a minor character. Her trans identity is acknowledged factually and respectfully by other characters, but it is not a central theme or source of conflict. She is depicted with agency, and her identity is neither uplifted nor denigrated, resulting in an incidental portrayal.

The show consistently portrays Heaven and its angelic inhabitants, who represent the ultimate 'good' in a Christian-inspired cosmology, as hypocritical, self-righteous, and often cruel. The narrative frequently satirizes the perceived moral superiority of these figures, presenting them as more flawed and less sympathetic than many of the Hell-born characters. This critique is aimed at institutionalized dogma and the abuse of power rather than individual faith.