The aim of this systematic review and meta-analysis was to provide an overview of existing controlled trials focusing on the impact of multiple family therapy (MFT) on mental health problems and family functioning, and to examine the efficacy of MFT. Relevant studies were selected following a screening of 3376 studies identified by a systematic search of seven databases. The following data were extracted: participant characteristics, program characteristics, study characteristics, and information of mental health problems and/or family functioning. A total of 31 peer-reviewed, English, controlled studies evaluating the effect of MFT were included in the systematic review. Sixteen studies presenting 16 trials were included in the meta-analysis. All but one of the studies was at risk of bias, with problems concerning confounding, selection of participants and missing data. The findings confirm that MFT is offered in diverse settings, with studies presenting a variety of therapeutic modalities, focal problems, and populations. Individual studies reported some positive findings, including improvements in mental health, vocational outcomes, and social functioning. The findings of the meta-analysis suggest that MFT is associated with improvements in symptoms of schizophrenia. However, this effect was found not to be significant due to the large amount of heterogeneity. In addition, MFT was associated with small improvements in family functioning. We found little evidence to suggest that MFT successfully alleviates mood and conduct problems. To conclude, more methodologically rigorous research is needed to further examine the potential benefits of MFT, as well as the working mechanisms and core components of MFT.