IntroductionThere are more than 370 million indigenous people from 5000 cultures living in 90 countries worldwide. Although they make up 5% of the global population, they account for 15% of the extreme poor. Youth suicide is the second leading cause of mortality among 15–29 years old and disproportionately affects indigenous youth. This research protocol pertains to a systematic review of studies that use a comparator/control group to evaluate the effectiveness of suicide interventions targeting indigenous adolescents (aged 10–19 years).Methods and analysisWe will conduct a systematic search on MEDLINE, EMBASE, CINAHL, LILACS and PsycINFO from inception to September 2019 to identify articles that compare mental health interventions for suicide prevention among indigenous adolescents. Two reviewers will independently determine the eligibility of each study. Studies will be assessed for methodological quality using the risk of bias tool to assess non-randomised studies of interventions. We will conduct a meta-analysis if possible and use established statistical methods to identify and control for heterogeneity where appropriate.Ethics and disseminationThis systematic review will use published data and does not require ethics approval. However, this review is in preparation of a feasibility study that will examine how best to support the physical and mental health of indigenous adolescents in Brazil. Ethics approval for the feasibility study was obtained from National Research Ethics Commission. Findings will be disseminated through a peer-reviewed publication and will be made available to key decision-makers with authority for indigenous health and other relevant stakeholders.PROSPERO registration numberCRD42019141754.