Physical exercise is increasingly recognized for its potential therapeutic effects in individuals with substance use disorders (SUDs), particularly in terms of relapse prevention, mental health improvement, and enhanced quality of life (QoL). This systematic review aimed to statistically summarize findings from numerous randomized controlled trials (RCTs) on the effects of physical exercise on mental health outcomes, QoL, abstinence-related outcomes, and cravings among SUD patients. A systematic search was conducted across PubMed, Web of Science, and Scopus databases, resulting in the inclusion of 15 studies, comprising RCTs, cohort studies, observational studies, and quasi-experimental designs. The review revealed a significant reduction in stress and depression, with a standardized mean difference (SMD) of 0.63, indicating a moderate effect size. Patients engaging in physical exercise reported a higher QoL across various domains, although the trend toward reduced cravings was not statistically significant, suggesting a need for further research in this area. The findings suggest that physical exercise can positively contribute to the treatment of SUD patients by enhancing mental health and QoL.