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Abstract Background Psychopathology and side effects of antipsychotic drugs contribute to worsening physical health and long-term disability, and increasing the risk of mortality in these patients. The efficacy of exercise on these factors is not fully understood, and this lack of knowledge may hamper the routine application of physical activity as part of the clinical care of schizophrenia. Aims To determine the effect of exercise on psychopathology and other clinical markers in patients with schizophrenia. We also looked at several moderators. Method MEDLINE, Web of Science, Scopus, CINAHL, SPORTDiscus, PsycINFO, and Cochrane Library databases were systematically searched from inception to October 2022. Randomized controlled trials of exercise interventions in patients 18–65 years old diagnosed with schizophrenia disorder were included. A multilevel random-effects meta-analysis was conducted to pool the data. Heterogeneity at each level of the meta-analysis was estimated via Cochran’s Q, I2, and R2. Results Pooled effect estimates from 28 included studies (1,460 patients) showed that exercise is effective to improve schizophrenia psychopathology (Hedges’ g = 0.28, [95% CI 0.14, 0.42]). Exercise presented stronger effects in outpatients than inpatients. We also found exercise is effective to improve muscle strength and self-reported disability. Conclusions Our meta-analysis demonstrated that exercise could be an important part in the management and treatment of schizophrenia. Considering the current evidence, aerobic and high-intensity interval training exercises may provide superior benefits over other modalities. However, more studies are warranted to determine the optimal type and dose of exercise to improve clinical outcomes in people with schizophrenia.