Mayans M.C. features multiple LGBTQ+ characters, including trans women and a bisexual woman, whose identities are integrated into the narrative without being a source of ridicule or degradation. While some characters face tragic outcomes, these are consistently framed as consequences of their dangerous lifestyle rather than their queer identity, reflecting a generally respectful and empathetic portrayal.

Mayans M.C. features Letty, a trans woman, as a recurring character. Her portrayal is complex and empathetic, particularly through her father Coco's journey of acceptance. The show affirms her worth, framing her challenges as external rather than inherent to her trans identity, resulting in a net positive impact.

The show portrays Catholicism as a deeply ingrained cultural and spiritual element for many characters, particularly those of Mexican descent. While individual characters may exhibit hypocrisy or struggle with their faith amidst violent lives, the narrative itself treats the religion and its iconography with a degree of respect, acknowledging its role in their heritage and personal struggles rather than condemning the faith as inherently negative.