Background: Pregnancy is associated with an increased risk for depression, anxiety, and insomnia. eHealth interventions provide a promising and accessible treatment alternative to face-to-face interventions., Objective: The objective of this systematic review and meta-analysis is to determine the effectiveness of eHealth interventions in preventing and treating depression, anxiety, and insomnia during pregnancy. Secondary aims are to identify demographic and intervention moderators of effectiveness., Methods: A total of 5 databases (PsycINFO, Medline, CINAHL, Embase, and Cochrane) were searched from inception to May 2021. Terms related to eHealth, pregnancy, randomized controlled trials (RCTs), depression, anxiety, and insomnia were included. RCTs and pilot RCTs were included if they reported an eHealth intervention for the prevention or treatment of depression, anxiety, or insomnia in pregnant women. Study screening, data extractions, and quality assessment were conducted independently by 2 reviewers from an 8-member research team (KAS, PRS, Hangsel Sanguino, Roshni Sohail, Jasleen Kaur, Songyang (Mark) Jin, Makayla Freeman, and Beatrice Valmana). Random-effects meta-analyses of pooled effect sizes were conducted to determine the effect of eHealth interventions on prenatal mental health. Meta-regression analyses were conducted to identify potential moderators., Results: In total, 17 studies were included in this review that assessed changes in depression (11/17, 65%), anxiety (10/17, 59%), and insomnia (3/17, 18%). Several studies included both depression and anxiety symptoms as outcomes (7/17, 41%). The results indicated that during pregnancy, eHealth interventions showed small effect sizes for preventing and treating symptoms of anxiety and depression and a moderate effect size for treating symptoms of insomnia. With the exception of intervention type for the outcome of depressive symptoms, where mindfulness interventions outperformed other intervention types, no significant moderators were detected., Conclusions: eHealth interventions are an accessible and promising resource for treating symptoms of anxiety, depression, and insomnia during pregnancy. However, more research is necessary to identify ways to increase the efficacy of eHealth interventions for this population., Trial Registration: PROSPERO (International Prospective Register of Systematic Reviews) CRD42020205954; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=205954., (©Katherine A Silang, Pooja R Sohal, Katherine S Bright, Jennifer Leason, Leslie Roos, Catherine Lebel, Gerald F Giesbrecht, Lianne M Tomfohr-Madsen. Originally published in JMIR Mental Health (https://mental.jmir.org), 21.02.2022.)