The Wayans Bros. frequently uses LGBTQ+ themes for comedic effect, often relying on harmful stereotypes and exaggerated portrayals. Instances of characters pretending to be gay or reacting with disgust to same-sex contact reinforce problematic tropes and homophobia, resulting in a net negative portrayal that lacks dignity or complexity.

The show frequently uses the 'man in drag' or 'transgender reveal' trope for comedic effect. These portrayals typically frame the discovery of a character's male identity as a source of shock and disgust for the male protagonists, contributing to a problematic and ridiculing depiction of gender non-conformity.

The show frequently incorporates Christian themes and values, particularly through characters like Grandma Ellington, who embodies traditional morality. While individual characters' religious practices might be subject to comedic exaggeration, the narrative generally treats Christianity with respect, aligning with its virtues of family, community, and moral guidance rather than portraying it as fundamentally oppressive or foolish.