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Indigenous Peoples experience disproportionately higher rates of problematic substance use. These problems are situated in a context of individual and intergenerational trauma from colonization, residential schools, and racist and discriminatory practices, policies, and services. Therefore, substance use interventions need to adopt a trauma-informed approach. We aimed to synthesize and report the current literature exploring the intersection of trauma and substance use interventions for Indigenous Peoples. Fourteen databases were searched using keywords for Indigenous Peoples, trauma, and substance use. Of the 1373 sources identified, 117 met inclusion criteria. Literature on trauma and substance use with Indigenous Peoples has increased in the last 5 years (2012-2016, n = 29; 2017-2021, n = 48), with most literature coming from the United States and Canada and focusing on historical or intergenerational trauma. Few articles focused on intersectional identities such as 2SLGBTQIA+ (n = 4), and none focused on veterans. There were limited sources (n = 25) that reported specific interventions at the intersection of trauma and substance use. These sources advocate for multi-faceted, trauma-informed, and culturally safe interventions for use with Indigenous Peoples. This scoping review illuminates gaps in the literature and highlights a need for research reporting on trauma-informed interventions for substance use with Indigenous Peoples.