ABSTRACT: BACKGROUND:Interpersonal psychotherapy (IPT) is a psychological intervention with established efficacy in the prevention and treatment of depressive disorders. Previous systematic reviews have not evaluated the effectiveness of IPT on symptoms of stress, anxiety, depression, quality of life, relationship satisfaction/quality, social supports, and an improved psychological sense of wellbeing. There is limited information regarding moderating and mediating factors that impact the effectiveness of IPT such as the timing of the intervention or the mode of delivery of IPT intervention. The overall objective of this systematic review was to evaluate the effectiveness of IPT interventions to treat perinatal (from pregnancy up to 12 months postpartum) psychological distress. METHODS:MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Cochrane Central Register of Controlled Trials (OVID), CINAHL with Full Text (Ebsco), Social Work Abstracts (Ebsco), SocINDEX with Full Text (Ebsco), Academic Search Complete (Ebsco), Family & Society Studies Worldwide (Ebsco), Family Studies Abstracts (Ebsco), and Scopus databases were searched from inception until 31 January 2019. Two researchers independently screened articles for eligibility. Of the 685 screened articles, 43 met the inclusion criteria. The search was re-run on 11 May 2020. An additional 204 articles were screened and two met the inclusion criteria, resulting in a total of 45 studies included in this review. There were 25 Randomized Controlled Trials, 10 Quasi-experimental studies, eight Open Trials, and two Single Case Studies. All included studies were critically appraised for quality. RESULTS:In most studies (n = 24, 53%), the IPT intervention was delivered individually; in 17 (38%) studies IPT was delivered in a group setting and two (4%) studies delivered the intervention as a combination of group and individual IPT. Most interventions were initiated during pregnancy (n = 27, 60%), with the remaining 18 (40%) studies initiating interventions during the postpartum period. LIMITATIONS:This review included only English-language articles and peer-reviewed literature. It excluded government reports, dissertations, conference papers, and reviews. This limited the access to grassroots or community-based recruitment and retention strategies that may have been used to target smaller or marginalized groups of perinatal women. CONCLUSIONS:IPT is an effective intervention for the prevention and treatment of psychological distress in women during their pregnancy and postpartum period. As a treatment intervention, IPT is effective in significantly reducing symptoms of depression and anxiety as well as improving social support, relationship quality/satisfaction, and adjustment. Systematic Review Registration: PROSPERO CRD42019114292.