BackgroundTo date, dozens of systematic reviews (SRs) and meta-analyses (MAs) summarize the effectiveness of preventive interventions for perinatal depression. However, the results are inconclusive, making an urgent need to step up to higher levels of evidence synthesis.AimsTo summarize and compare the evidence from the SR&MA examining the effectiveness of all types of interventions for preventing perinatal depression.MethodPubMed, PsycINFO, Cochrane Database of Systematic Reviews and OpenGrey were searched from inception to December 2022. We selected SR&MA of randomized controlled trials (RCTs) that compared all types of preventive interventions for perinatal depression with control groups whose outcome was the reduction of depressive symptoms and/or incidence of new cases of perinatal depression (PROSPERO: CRD42020173125).ResultsA total of 19 SRs and MAs evaluated 152 unique RCTs that included 83,408 women from 26 countries and five continents. The median effect size for any intervention was SMD = 0.29 (95% CI: 0.20 to 0.38). Exercise/physical activity-based, psychological, and any type of intervention showed median effect sizes of 0.43, 0.28 and 0.36, respectively. The degree of overlap among RCTs was slight. According to AMSTAR-2, 79% of them were rated as low or critically low-quality. The strength of evidence, according to GRADE, was poorly reported and, in most cases, was low.ConclusionsExercise/physical activity-based and psychological interventions have a small-to-medium effect on reducing perinatal depressive symptoms. There is insufficient evidence to conclude that dietary supplements and pharmacological interventions are effective in preventing perinatal depression. There is a need for high-quality SR&MA of RCTs, mainly focusing on universal preventive interventions.