American Indians and Alaska Natives suffer from disproportionately high rates of chronic mental and physical health conditions. These health inequities are linked to colonization and its downstream consequences. Most of the American Indian and Alaska Native health inequities research uses a deficit framework, failing to acknowledge the resilience of American Indian and Alaska Native people despite challenging historical and current contexts. This scoping review is based on a conceptual model which acknowledges the context of colonization and its consequences (psychological and health risk factors). However, rather than focusing on health risk, we focus on protective factors across three identified domains (social, psychological, and cultural/spiritual), and summarize documented relationships between these resilience factors and health outcomes. Based on the scoping review of the literature, we note gaps in extant knowledge and recommend future directions. The findings summarized here can be used to inform and shape future interventions which aim to optimize health and well-being in American Indian and Alaska Native peoples.