Lou Grant addressed LGBTQ+ themes in the late 1970s, notably in the episode "Gangs." This episode depicted a gay character as a victim of a hate crime, with the narrative focusing on the injustice and the newspaper's empathetic investigation. The portrayal was considered sensitive and affirming for its time, framing prejudice as an external societal issue and advocating for dignity and justice.

The 'Lou Grant' episode 'Hooker' features a transsexual character as a murder victim, handled with a progressive and empathetic tone for its era. The narrative seriously investigates the challenges and prejudice faced by the character, framing them as external societal issues. This portrayal, while tragic, affirms the worth of transsexual lives by treating the subject with dignity and aiming for understanding.

The series, known for its nuanced exploration of social issues, portrays Christian characters and themes with depth and respect. While it may critique individual hypocrisy or institutional failings, the narrative generally affirms the dignity of faith and condemns bigotry against it.

Consistent with its humanistic approach, 'Lou Grant' depicts Jewish characters and cultural aspects with respect and nuance. The show focuses on individual experiences and societal challenges, avoiding negative stereotypes and often highlighting the strength and resilience found within the community.