The arts and humanities have enriched human life in various ways throughout history. Yet, an analysis of empirical research into the effects of arts and humanities engagement remains incomplete, calling for a systematic and integrative understanding of the role of arts and humanities in promoting human flourishing. The present study used a mixed studies systematic review approach to integrating recent evidence from 27 intervention studies on the effectiveness of arts and humanities interventions on psychological flourishing of healthy adults. Our final dataset both represented quantitative and qualitative data on real-world interventions that encompassed a range of arts and humanities domains, including music, theater, visual arts, and integrative arts. A separate quantitative and qualitative data synthesis on study characteristics and psychological flourishing outcomes and a meta-integration of both types of evidence were conducted. Overall, arts and humanities interventions were associated with positive changes in a range of psychological flourishing outcomes, with overlapping quantitative and qualitative evidence for emotional, social, and sense of self outcomes. A secondary analysis explored key contextual and implementation features that contributed to effectiveness. Recommendations for future research and practice are provided based on our review.