ABSTRACT: Although 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.We 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.We 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.Out 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<.001, median 1.47, 95% CI 2.36-0.59) and moods and feelings (2 studies; P=.04, median 5.55, 95% CI 10.88-0.22) improved as well in the Web-based intervention group, but there was no difference in stress scores. However, adolescents in the intervention group left the study early more often, both in short-term studies (11 studies; P=.007, median 1.31, 95% CI 1.08-1.58) and mid-term studies (3 studies; P=.02, median 1.65, 95% CI 1.09-2.49). We did not find any studies that had assessed the costs of the Web-based interventions.Despite widely reported promises that information technology use is beneficial to adolescents with depression, the results of our review show only short-term effects on adolescents' mental well-being, whereas long-term effects remain questionable because of the limited number of studies reviewed. Information about the economic benefits of Web-based interventions is still lacking. The quality of the studies, especially biases related to attrition rates and selective reporting, still needs serious attention.