Hightown features lesbian protagonists Jackie Quiñones and Renee Segna, whose complex relationships and personal struggles are central to the narrative. The show portrays their queer identities with dignity and agency, integrating them naturally into the story without making their sexuality the source of their problems or depicting it negatively. Their same-sex relationships are normalized and treated with dramatic realism.

Hightown features Daisy, a trans woman, whose story is largely defined by drug addiction, sex work, and a violent death. This portrayal reinforces problematic stereotypes and the 'dead trans woman' trope. Despite her connection to a main character, the narrative offers little positive affirmation, leading to a net negative impact due to the unrelieved misery and punitive outcome.