Highlights• Indigenous Peoples are concerned with previous experience of substance use research as disempowering.• Community psychology principles may inform ethical community-driven substance use research.• We explore these principles through seven Indigenous substance use studies across the U.S. and Canada.• Indigenous substance use research reflects, expands, and challenges community psychology principles.• We discuss implications for Indigenous substance use research and community psychology.Abstract Many Indigenous communities are concerned with substance use (SU) problems and eager to advance effective solutions for their prevention and treatment. Yet these communities also are concerned about the perpetuation of colonizing, disorder-focused, stigmatizing approaches to mental health, and social narratives related to SU problems. Foundational principles of community psychology-ecological perspectives, empowerment, sociocultural competence, community inclusion and partnership, and reflective practice-provide useful frameworks for informing ethical community-based research pertaining to SU problems conducted with and by Indigenous communities. These principles are explored and extended for Indigenous community contexts through themes generated from seven collaborative studies focused on understanding, preventing, and treating SU problems. These studies are generated from research teams working with Indigenous communities across the United States and Canada-inclusive of urban, rural, and reservation/reserve populations as well as adult and youth participants. Shared themes indicate that Indigenous SU research reflects community psychology principles, as an outgrowth of research agendas and processes that are increasingly guided by Indigenous communities. At the same time, this research challenges these principles in important ways pertaining to Indigenous-settler relations and Indigenous-specific considerations. We discuss these challenges and recommend greater synergy between community psychology and Indigenous research.