Background and AimsSubstance use among medical students may have consequences like poor academic performance and impaired patient care. There is a growing literature on substance use among medical students in India. This systematic review and meta-analysis were done to synthesize the literature on substance use among medical students in India.MethodsMedline and Google Scholar were used as search engines to ascertain the literature that reported substance use among Indian medical students from January 2000 to January 2022. The pooled prevalence of tobacco, alcohol, other substance, and overall substance use was computed.ResultsA total of 65 studies were included. The pooled prevalence of tobacco use was 21.9% (95% confidence intervals [CI] 18.5% to 25.3%, n = 20,165, k = 51), while the pooled prevalence of alcohol use was 27.1% (95% CI of 23.0% to 31.1%, n = 11,823, k = 31). The overall pooled prevalence of substance use was 40.3% (95% CI of 25.5% to 55.2%, n = 4960, k = 10), while pooled prevalence of cannabis was 8.2% (95% CI of 4.9% to 11.5%, n = 2418, k = 7). The use of tobacco was about 10 times higher in males than females, while the odds of alcohol use were about five times higher in males.ConclusionSubstance use is common among medical students, with rates of substance use being generally higher in males as compared to females. Targeted interventions may help to reduce substance use and prevent the development of substance use disorders in this population.