Background: Frequent Cannabis use has been linked to a variety of negative mental, physical, and social consequences. We assessed the effects of digital prevention and treatment interventions on Cannabis use reduction in comparison with control conditions. Methods: Systematic review with two separate meta-analyses. Thirty randomized controlled trials met the inclusion criteria for the review, and 21 were included in the meta-analyses. Primary outcome was self-reported Cannabis use at post-treatment and follow-up. Hedges's g was calculated for all comparisons with non-active control. Risk of bias was examined with the Cochrane risk-of-bias tool. Results: The systematic review included 10 prevention interventions targeting 8138 participants (aged 12 to 20) and 20 treatment interventions targeting 5195 Cannabis users (aged 16 to 40). The meta-analyses showed significantly reduced Cannabis use at post-treatment in the prevention interventions (6 studies, N = 2564, g = 0.33; 95% CI 0.13 to 0.54, p = 0.001) and in the treatment interventions (17 comparisons, N = 3813, g = 0.12; 95% CI 0.02 to 0.22, p = 0.02) as compared with controls. The effects of prevention interventions were maintained at follow-ups of up to 12 months (5 comparisons, N = 2445, g = 0.22; 95% CI 0.12 to 0.33, p < 0.001) but were no longer statistically significant for treatment interventions. Conclusions: Digital prevention and treatment interventions showed small, significant reduction effects on Cannabis use in diverse target populations at post-treatment compared to controls. For prevention interventions, the post-treatment effects were maintained at follow-up up to 12 months later.