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BackgroundDepression and anxiety contribute to an estimated 74.6 million years of life with disability, and 80% of this burden occurs in low- and middle-income countries (LMICs), where there is a large gap in care. ObjectiveWe aimed to systematically synthesize available evidence and quantify the effectiveness of digital mental health interventions in reducing depression and anxiety in LMICs. MethodsIn this systematic review and meta-analysis, we searched PubMed, Embase, and Cochrane databases from the inception date to February 2022. We included randomized controlled trials conducted in LMICs that compared groups that received digital health interventions with controls (active control, treatment as usual, or no intervention) on depression or anxiety symptoms. Two reviewers independently extracted summary data reported in the papers and performed study quality assessments. The outcomes were postintervention measures of depression or anxiety symptoms (Hedges g). We calculated the pooled effect size weighted by inverse variance. ResultsAmong 11,196 retrieved records, we included 80 studies in the meta-analysis (12,070 participants n=6052, 50.14% in the intervention group and n=6018, 49.85% in the control group) and 96 studies in the systematic review. The pooled effect sizes were −0.61 (95% CI −0.78 to −0.44; n=67 comparisons) for depression and −0.73 (95% CI −0.93 to −0.53; n=65 comparisons) for anxiety, indicating that digital health intervention groups had lower postintervention depression and anxiety symptoms compared with controls. Although heterogeneity was considerable (I2=0.94 for depression and 0.95 for anxiety), we found notable sources of variability between the studies, including intervention content, depression or anxiety symptom severity, control type, and age. Grading of Recommendations, Assessments, Development, and Evaluation showed that the evidence quality was overall high. ConclusionsDigital mental health tools are moderately to highly effective in reducing depression and anxiety symptoms in LMICs. Thus, they could be effective options to close the gap in depression and anxiety care in LMICs, where the usual mental health care is minimal. Trial RegistrationPROSPERO CRD42021289709; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=289709