BACKGROUND: People with substance use disorder (SUD) are at significantly greater risk of suicide compared with the general population. In recent years the number of suicides resulting from drug poisoning in England and Wales has increased. We sought to identify and evaluate the effect of interventions to prevent suicide or reduce self-harm among people with SUD. METHODS: We conducted a systematic review of randomised controlled trials (RCTs) of interventions for people with SUD that included suicide or self-harm-related primary outcomes. We searched Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, PubMed, Embase and Web of Science from inception until 13th January 2019. Studies were assessed for bias using the Cochrane Risk of Bias 2 tool. A random effects meta-analysis of standardised mean differences (SMD) was conducted. RESULTS: We identified six RCTs from four countries (Australia, Iran, the United States of America and the United Kingdom) comprising 468 participants in total. All but one study investigated psychosocial interventions. On average across studies there was weak evidence of a small positive effect of interventions on suicide or self-harm outcomes (d=-0.20, 95% CI=-0.39-0.00). LIMITATIONS: Studies were heterogeneous in terms of population, intervention, controls and outcome. There were some concerns regarding bias for all trials. All trials were liable to type II error. CONCLUSIONS: Evidence is currently lacking regarding the effectiveness of interventions to prevent suicide and reduce self-harm amongst people with SUD.