Cloud Atlas features a significant and emotionally resonant portrayal of a bisexual character, Robert Frobisher, and his love for Rufus Sixsmith. Despite a tragic end, their relationship is depicted with dignity and complexity, affirming the worth and enduring nature of their bond across time. The film's stance is empathetic and validating.

The film, an adaptation of the novel, intentionally features actors portraying multiple characters across different time periods and races. Several characters, whose race was established in the source material (e.g., Korean characters played by white or Black actors, or white characters played by Black actors), are depicted on screen by actors of a different race, often through extensive makeup.

The film's central themes of reincarnation, interconnectedness, and enlightenment, particularly through Sonmi~451's journey and teachings, strongly align with Buddhist philosophy. Her message is portrayed as a positive, liberating force for humanity.

The film depicts institutions and adherents associated with Christianity engaging in hypocrisy, slavery, and oppressive control (e.g., the 1849 slave trade, the 2012 nursing home). The narrative offers no significant counterbalancing positive portrayal of the faith itself.