Background: Fetal alcohol spectrum disorder (FASD) is a preventable, lifelong neurodevelopmental disorder caused by prenatal alcohol exposure. FASD negatively impacts individual Indigenous communities around the world. Although many prevention interventions have been developed and implemented, they have not been adequately evaluated. This systematic review updates the evidence for the effectiveness of FASD prevention interventions in Indigenous/Aboriginal populations internationally, and in specific populations in North America and New Zealand, and offers recommendations for future work. Method: The MEDLINE, Embase, CINAHL Plus, Web of Science, PsycINFO, SocINDEX, and Informit databases were searched from inception to 22/08/2017 for all prevention and intervention papers published in peer-reviewed scientific journals, with results, targeting prenatal alcohol exposure and FASD in Indigenous populations. This review was limited to studies published in English and excluded interventions focusing on the workforce. All steps were completed independently by two reviewers with discrepancies resolved via consensus with the senior author. Results: There was significant heterogeneity in the ten included studies. Populations targeted included non-pregnant women of child-bearing age, pregnant women, school children and the general public. Study designs included one randomised controlled trial, five cohort studies with pre-post design, one cross-sectional study with different pre- and post-intervention groups, and four studies collected post-intervention data. Studies assessed changes in knowledge, and/or changes in risk for prenatal alcohol exposure including self-reported alcohol consumption, use of birth control or a combination of both. One study was conducted in Australia and nine in the US. The methodological quality of all studies was rated as 'Poor' using the systematic review assessment tools developed by The National Heart, Lung and Blood Institute. Studies were subject to substantial bias due to issues such as high loss to follow-up, lack of control groups and the reliance on self-report measures to assess the main outcome. Conclusion: Overall, there is little evidence that previous interventions aiming to reduce the risk of prenatal alcohol exposure or FASD in Indigenous populations have been effective. Future intervention studies should address the cultural factors and historical context that are fundamental to successful work with Indigenous populations, and be designed, implemented and evaluated using rigorous methods. This systematic review was registered with PROSPERO, CRD42018086212.