BackgroundAlthough previous studies on information and communication technology (ICT)–based intervention on mental health among adolescents with depressive symptoms have already been combined in a number of systematic reviews, coherent information is still missing about interventions used, participants’ engagement of these interventions, and how these interventions work. ObjectiveWe conducted a systematic review and meta-analysis of trials to describe the effectiveness of Web-based interventions to support adolescents with depression or depressive symptoms, anxiety, and stress. We also explored the content of the interventions, as there has previously been a lack of coherent understanding of the detailed content of the Web-based interventions for these purposes. MethodsWe included parallel randomized controlled trials targeted at adolescents, or young people in the age range of 10 and 24 years, with symptoms or diagnoses of depression and anxiety. The interventions were from original studies aimed to support mental health among adolescents, and they were delivered via Web-based information and communication technology. ResultsOut of 2087 records identified, 27 papers (22 studies) met the inclusion criteria. On the basis of a narrative analysis of 22 studies, a variety of Web-based interventions were found; the most commonly used intervention was based on cognitive behavioral therapy. Meta-analysis was further conducted with 15 studies (4979 participants). At the end of the intervention, a statistically significant improvement was found in the intervention group (10 studies) regarding depressive symptoms (P=.02, median 1.68, 95% CI 3.11-0.25) and after 6 months (3 studies; P=.01, median 1.78, 95% CI 3.20-0.37). Anxiety symptoms (8 studies; P