Chicago Hope included multiple LGBTQ+ storylines, particularly in later seasons, featuring HIV-positive gay men, lesbian couples, and a transgender patient. These portrayals generally approached queer identities with dignity and empathy, framing obstacles as external societal issues rather than inherent flaws, resulting in a net positive impact.

Chicago Hope featured a groundbreaking episode in 1995 depicting a patient seeking and undergoing sex reassignment surgery. The narrative portrays the transsexual character with dignity and agency, focusing on her journey and the medical team's ethical considerations. The show ultimately affirms the patient's identity and the validity of the procedure, presenting a supportive and empathetic portrayal for its time.

The series typically explores Christian faith as a significant aspect of characters' lives, providing comfort, moral guidance, and community. While individual interpretations might lead to conflict, the narrative generally treats the religion with respect and nuance.

Judaism is often depicted through patient and staff storylines, highlighting its cultural, ethical, and spiritual importance. The show portrays Jewish traditions and beliefs with dignity and sensitivity, exploring their role in personal and medical decisions.