The disproportionate burden of mental illness experienced by Indigenous adolescents is well established. Therefore, this review focused on how the well-being of Indigenous adolescents can be better promoted. The review identified studies that examined the relationship between cultural engagement and psychological well-being among Indigenous adolescents. To achieve this, a systematic search of published literature across seven online databases including Medline and EMBASE was conducted between October and November 2020. To meet the inclusion criteria, studies were required to include a sample of Indigenous adolescents and measure the relationship between psychological well-being and cultural engagement. Twenty-five studies met the inclusion criteria, yielding a total sample size of 19,231 participants. Eighteen studies (72%) reported a significant positive relationship between cultural engagement and psychological well-being, four studies (16%) reported a nonsignificant relationship, and three studies (12%) reported mixed findings. Despite measuring different domains of culture across the 25 studies, these findings demonstrate relatively strong evidence of a positive association between cultural engagement and psychological well-being. They highlight the importance of culture for young Indigenous Peoples in developing a positive well-being. In the future, researchers should focus on specifying how intervention factors contribute to cultural engagement effects and establish further contributors to well-being and positive development among Indigenous adolescents. The findings of this review advance our understanding of how Indigenous Peoples interpret culture and their engagement with this culture. This has implications for policy, programs, and interventions intended to enhance well-being outcomes for Indigenous communities.