Background Substance use amongst young people poses developmental and clinical challenges, necessitating early detection and treatment. Considering the widespread use of technology in young people, delivering interventions digitally may help to reduce and monitor their substance use. Aims We conducted a systematic review and two meta-analyses to assess the effectiveness of digital interventions for reducing substance use (alcohol, smoking, and other substances) among young people aged 10 to 24 years old. Method Embase, Global Health, Medline, PsychINFO, Web of Science and reference lists of relevant papers were searched in November 2020. Studies were included if they quantitatively evaluated the effectiveness of digital health technologies for treating substance use. A narrative synthesis and meta-analysis were conducted. Results Forty-two studies were included in the systematic review and 18 in the meta-analyses. Digital interventions showed small, but statistically significant reductions in weekly alcohol consumption compared to controls (SMD= −0.12, 95% CI= −0.17 to −0.06, I2 =0%), but no overall effect was seen on 30-day smoking abstinence (OR = 1.12, 95% CI = 0.70 to 1.80, I2 =81%). The effectiveness of digital interventions for reducing substance use is generally weak, however, promising results such as reducing alcohol use were seen. Large-scale studies should investigate the viability of digital interventions, collect user feedback, and determine cost-effectiveness. Prisma/Prospero This systematic review was conducted following Cochrane methodology PRISMA guidelines. The review was registered with PROSPERO in November 2020 (CRD42020218442).