Purpose Subjective and objective social isolation are important factors contributing to both physical and mental health problems, including premature mortality and depression. This systematic review evaluated the current evidence for the effectiveness of interventions to improve subjective and/or objective social isolation for people with mental health problems. Primary outcomes of interest included loneliness, perceived social support, and objective social isolation. Methods Three databases were searched for relevant randomised controlled trials (RCTs). Studies were included if they evaluated interventions for people with mental health problems and had objective and/or subjective social isolation (including loneliness) as their primary outcome, or as one of a number of outcomes with none identified as primary. Results In total, 30 RCTs met the review’s inclusion criteria: 15 included subjective social isolation as an outcome and 11 included objective social isolation. The remaining four evaluated both outcomes. There was considerable variability between trials in types of intervention and participants’ characteristics. Significant results were reported in a minority of trials, but methodological limitations, such as small sample size, restricted conclusions from many studies. Conclusion The evidence is not yet strong enough to make specific recommendations for practice. Preliminary evidence suggests that promising interventions may include cognitive modification for subjective social isolation, and interventions with mixed strategies and supported socialisation for objective social isolation. We highlight the need for more thorough, theory-driven intervention development and for well-designed and adequately powered RCTs.