The U.S. is experiencing an alarming opioid epidemic, and although American Indians and Alaska Natives (AI/ANs) are especially hard hit, there is a paucity of opioid-related treatment research with these communities. AI/ANs are second only to Whites in the U.S. for overdose mortality. Thus, the National Institute on Drug Abuse convened a meeting of key stakeholders to elicit feedback on the acceptability and uptake of medication assisted treatment (MAT) for opioid use disorders (OUDs) among AI/ANs. Five themes from this one-day meeting emerged: 1) the mismatch between Western secular and reductionistic medicine and the AI/AN holistic healing tradition; 2) the need to integrate MAT into AI/AN traditional healing; 3) the conflict between standardized MAT delivery and the traditional AI/AN desire for healing to include being medicine free; 4) systemic barriers; and 5) the need to improve research with AI/ANs using culturally relevant methods. Discussion is organized around key implementation strategies informed by these themes and necessary for the successful adoption of MAT in AI/AN communities: 1) type of medication; 2) educational interventions; 3) coordination of care; and 4) adjunctive psychosocial counseling. Using a community-based participatory research approach is consistent with a “two eyed seeing” approach that integrates Western and Indigenous worldviews. Such an approach is needed to develop impactful research in collaboration with AI/AN communities to address OUD health disparities. •AI/ANs exhibit alarming opioid use disorder (OUD) related health disparities.•MAT implementation with AI/ANs requires integrating MAT into traditional healing.•Some barriers to MAT implementation involve unique cultural considerations.•A “two-eyed seeing” approach uses both Western and indigenous worldviews.•Collaborative research is needed to address the AI/AN OUD health disparities.