Midnight, Texas features prominent gay characters, Joe and Chuy Strong, whose loving, long-term relationship is a stable and respected part of the narrative. Their sexuality is depicted with dignity and is not a source of conflict or negative stereotypes. Other LGBTQ+ characters are also presented positively, contributing to an overall affirming and integrated portrayal within the show's supernatural setting.

The show features multiple instances of race swaps from its source novels. Fiji Cavanaugh, depicted as white in the books, is portrayed by a biracial actress. Lemuel Bridger, described as white in the books, is portrayed by a Black actor.

The series consistently portrays organized or fundamentalist Christianity as a source of bigotry, persecution, and danger for the supernatural community. Religious zealots and institutions are frequently depicted as antagonists, driving the narrative's conflict through their intolerance and violence against those who are different.