Queen of the South features multiple LGBTQ+ characters whose identities are integrated naturally into the narrative. Their relationships and personal lives are depicted with dignity and complexity, without their sexuality being a source of mockery, villainy, or the cause of their suffering. The show's stance remains respectful and empathetic, leading to a net positive portrayal.

Queen of the South features La Capitana, a transgender woman who is a prominent figure in a drug cartel. Her identity is present and acknowledged but not central to the narrative, avoiding both strong positive affirmation and negative stereotyping, thus resulting in a neutral portrayal.

The show features Teresa Mendoza, who, despite primarily using firearms, engages in a direct physical confrontation where she uses a knife to defeat a male assailant in close combat.

The show consistently portrays adherents of Christianity, particularly Catholicism, as deeply hypocritical. Characters frequently invoke God, wear religious symbols, and pray while engaging in extreme violence, drug trafficking, and murder, without the narrative offering a counterbalancing positive view of the faith's virtues.