Aims <p>To assess the effect of music therapy in improving chronic pain (CP), anxiety, depression, and quality of life using randomized controlled trials, and to explore the role of various moderators in MT effectiveness.</p> Design <p>Systematic review and Meta-analysis.</p> Methods <p>We systematically searched four electronic databases for randomized controlled trials that investigated the effects of music therapy on chronic pain, anxiety, depression, and quality of life. We performed a Cochrane risk-of-bias assessment and calculated the pooled standard mean difference in the outcomes of the test and control groups after the intervention period.</p> Results <p>Nine randomized controlled trials were retrieved that included a total of 787 patients. Music therapy significantly reduced CP in the test group compared with that in the control group post-intervention and depression, no evidence was observed for improvement in anxiety and quality of life. Subgroup analysis reveals that MT is most effective when interventions are conducted in developed countries, targeting CNMP or cancer pain patients in health centers. The therapy is most effective when patients select their own music, use instruments or earphones, and receive treatment from trained professionals, with an ideal duration of 20&#xa0;min, except in studies involving postoperative CP or those conducted in developing countries.</p> Conclusions <p>Music therapy effectively reduces CP and depression, but has limited effects on anxiety and quality of life. Its effectiveness varies depending on the specific conditions and CP categories of patients, with differences observed between developing and developed countries. Future research should focus on developing standardized guidelines for music therapy, exploring its long-term effects on pain, anxiety, and quality of life, and conducting high-quality, multicenter RCTs in developing countries to support its global adoption in CP management.</p>