Clerks II features a transgender character, Lance Dowds, whose identity is revealed in a scene played for shock-comedy. While Dante offers a mild acceptance, Randal reacts with extreme transphobia and uses slurs, which forms the primary comedic thrust of the interaction. The film uses the character's identity as a source of problematic humor without strong narrative critique, leading to a net negative portrayal.

Clerks II includes a brief comedic scene with a transsexual character. The portrayal is problematic due to a main character's transphobic reaction, including the use of a derogatory slur, which is presented for humor without significant narrative critique or counterbalance, leading to a net negative impact.

The film features Elias, a devout Catholic, who is frequently the target of Randal's cynical and bigoted jokes. However, the narrative consistently frames Randal's anti-religious remarks as ignorant and offensive, positioning the audience to sympathize with Elias and his genuine faith. The film satirizes religious hypocrisy and commercialization but ultimately affirms the dignity of sincere belief.

References to Judaism primarily come from Randal's insensitive and stereotypical jokes. The film uses these comments to highlight Randal's bigotry and ignorance, rather than to portray Judaism itself negatively. The narrative clearly condemns Randal's prejudiced remarks.