Painting therapy has become an important approach to the treatment of depression in adolescents. However, depressed adolescents face low self-confidence, low engagement, and self-absorption when undergoing painting therapy. Informed by need-finding investigations, We developed Realms of the Heart, a human-AI collaborative gamified complementary treatment system for depressed adolescents. Realms of the Heart includes two AI-driven strategies: the transformation of natural objects collected by teens’ exploration into brushes, and the generation of sketches corresponding to natural objects by using brushes based on ControlNet. We conducted a randomized controlled trial. Participants were randomized into an experimental group and a control group. The results showed that Realms of the Heart increased users’ motivation and significantly alleviated their level of depression. These findings not only shed light on the role of human-AI co-created painting therapy in the treatment of adolescent depression but also pave the way for more informed design strategies for art therapy.