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Objective To review available literature and identify the experimental evidence for effective treatment of depression in Indigenous populations worldwide. Method MEDLINE, EMBASE, PsychInfo, Informit, Psychology, and Behavioural Sciences databases were systematically searched for intervention studies from each database's inception to November 2016. Randomised controlled trials were included if they examined the effects of therapy for depression as primary or secondary outcome with Indigenous participants of any age group. Results This review found a total of four experimental trials (152 participants) worldwide studying the effect of behavioural and pharmacological interventions for depression in Indigenous populations. The quality of evidence was low to moderate. Results from three diverse interventions suggest that culturally specific cognitive and behavioural therapy may have the potential to reduce depressive symptoms in Indigenous young people. However, the evidence base is currently insufficient to offer sound conclusions. One trial studied the effect of dosage differences (75 vs 125 mg) of a tricyclic antidepressant, clomipramine, finding that Indigenous African patients may respond to treatment regimens at a lower dosage than recommended standard in western textbooks. Conclusions Findings from this review indicate potential for the use of culturally adapted behavioural interventions to target depression in Indigenous populations; however, current evidence is insufficient to confirm their effectiveness. Similarly, there is insufficient evidence to propose recommendations for effective pharmacological treatment for Indigenous people. A tentative finding, that lower doses of antidepressants might be effective for the Indigenous, compared to the general population, requires further investigation as it holds important implications for clinical practice. More rigorous experimental research with adequate sample sizes needs to be conducted to provide conclusive recommendations for adoption into standard care.