Recently, we see a sharp increase in the number of multi-component positive psychology interventions (MPPIs). The aim of the current study is to examine the efficacy of MPPIs, through a systematic review and meta-analysis. We included 50 randomized controlled trials that were published in 51 articles between 1998 and August 2018. We found standardized mean differences of Hedges’ g = 0.34 for subjective well-being, Hedges’ g = 0.39 for psychological well-being, indicating small to moderate effects, and Hedges’ g = 0.29 for depression, and Hedges’ g = 0.35 for anxiety and stress, indicating small effects. Removing outliers led to a considerable decrease in effect sizes for subjective well-being and depression, a slight decrease for psychological well-being, and a strong increase in the effect size for stress. Removing low quality studies led to a considerable decrease in the effect sizes for subjective well-being, psychological well-being, and depression, and a slight decrease for anxiety, but a strong increase for stress. Moderator analyses only showed a significant effect for study quality, showing larger effect sizes for low quality studies compared to studies of moderate and high quality. In addition, a larger effect size for anxiety was found in studies from non-Western countries compared to studies from Western countries. In sum, this systematic review and meta-analysis found evidence for the efficacy of MPPIs in improving mental health. We conclude that MPPIs have a small effect on subjective well-being and depression, and a small to moderate effect on psychological well-being. In addition, they may have a small to moderate effect on anxiety and a moderate effect on stress, but definite conclusions of the effects of MPPIs on these outcomes cannot me made due to the limited number of studies. Further well-conducted research among diverse populations is necessary to strengthen claims on the efficacy of MPPIs.