Background: Prevention of antenatal and postnatal depression is crucial, given its high prevalence and severe consequences. Although several systematic reviews and meta-analyses have examined the effects of psychological interventions on the population at risk for perinatal depression, few studies have focused on universal prevention and none have focused specifically on universal prevention in pregnancy. The aim of this study is to examine the effects of psychological interventions with a universal prevention focus on perinatal depression during pregnancy by performing a systematic review and meta-analysis based on both the latest articles and a broader literature search. Methods: The literature search will be conducted using the Cochrane Controlled Register of Trials (CENTRAL), Embase, PubMed and PsycINFO, from inception onwards. Randomized controlled trials that examined the association between psychological interventions and universal prevention of antenatal and postnatal depression among pregnant women will be included. Study selection, data collection, quality assessment, and statistical syntheses will be conducted following a priori defined methods in the protocol. Discussion: The findings of this systematic review and meta-analysis will have both clinical and political importance in the context of perinatal mental health. In addition, this study will promote future studies and clarify the direction of research on universal prevention of perinatal depression. Systematic review registration: PROSPERO CRD42019118041