BACKGROUND: The legacies of colonization and of policies of forced assimilation continue to be a cause of intergenerational trauma, manifested through feelings of marginality, depression, anxiety and confusion, which place indigenous peoples at increased risk of suicide. OBJECTIVES: To assess the quality, content, delivery and effectiveness of interventions for preventing suicides among indigenous adolescents. DESIGN AND SETTING: Systematic review conducted with Cochrane methodology, Campo Grande, Mato Grosso do Sul, Brazil. METHODS: The Cochrane library, MEDLINE, EMBASE, CINAHL, LILACS and PsycINFO databases were searched for studies published up to February 2021. The following inclusion criteria were used: published in any language; interventions that aimed to prevent suicides among indigenous adolescents; randomized or non-randomized study with a control or comparative group; and validated measurements of mental health problems. RESULTS: Two studies were identified: one on adolescents in the remote Yup'ik community in south-western Alaska, and the other on Zuni adolescents in New Mexico. Both studies showed evidence of effectiveness in interventions for reducing some of the risk factors and increasing some of the protective factors associated with suicide. High levels of community engagement and culture-centeredness were key anchors of both studies, which ensured that the intervention content, delivery and outcome measurements aligned with the beliefs and practices of the communities. Both studies were judged to have a moderate risk of bias, with biases in sample selection, attrition and inadequate reporting of results. CONCLUSIONS: The current evidence base is small but signaled the value of culturally appropriate interventions for prevention of suicide among indigenous adolescents. REGISTRATION DETAILS: The study protocol is registered in the international prospective register of systematic reviews (PROSPERO); no. CRD42019141754.