Background: The high prevalence and severe consequences of antenatal and postnatal depression makes their prevention critical. Previous systematic reviews and meta-analysis have shown the effects of psychological interventions on perinatal depression in individuals at risk. However, none have focused explicitly on universal prevention in the antenatal period. The purpose of this study is to conduct a systematic review and meta-analysis to clarify the effects of antenatal psychological interventions on perinatal depression, specifically focusing on universal prevention. Methods: Four electronic databases, the Cochrane Controlled Register of Trials (CENTRAL), Embase, PubMed, and PsycINFO, were used to search for published randomized controlled trials from inception to January 28, 2019. Twelve investigators conducted the first screening from title and abstract, individually, and then NY and ZN performed full-text review one by one. For the meta-analysis, a random effect model was conducted by using Review Manager 5.3 for Windows. Subgroup analyses were also conducted for studies that employed a cognitive behavioral (CB) based approach. Results: A total of 13,026 studies were initially searched. After removing duplicates, 9,919 studies were screened, and finally 18 studies met the inclusion criteria. The meta-analysis showed a significant effect of antenatal psychological intervention on both antenatal and postnatal depression (SMD = 0.28, 95% CI = 0.11 to 0.44, SMD = 0.37, 95% CI = 0.08 to 0.66) with moderate to high level of heterogeneity (I2 = 61%, p = 0.01; I2 = 84%, p < 0.001). For subgroup analysis, a significant effect of a CB based approach on antenatal depression was found in an antenatal period (SMD = 0.53, 95% CI = 0.13 to 0.94) with high heterogeneity (I2 = 85%, p = 0.001), while non-significant results were shown on postnatal depression (SMD = 0.45, 95% CI = -0.03 to 0.92). Limitations: Limitations include a language bias, as we included only studies published in English, and that the assessment of antenatal and postnatal depression using different methods caused high heterogeneity across studies. Conclusions: Psychological intervention in an antenatal period could be effective for universal prevention of both antenatal and postnatal depression. However, the results were still inconclusive due to relatively low methodological quality in the included studies. The evidence from more well-designed trials is needed in future studies.