A systematic review and meta-analysis of 40 randomized controlled trials (RCTs) found that exercise significantly improves balance, walking ability, walking endurance, fatigue, and quality of life in people with multiple sclerosis (MS). Exercise interventions, including aerobic exercise, resistance exercise, and multicomponent training, were effective in reducing fatigue, with resistance exercise being the most effective. Aerobic exercise was most effective in improving quality of life. Younger participants showed greater improvements in fatigue. The study highlights that resistance and aerobic exercise are the most effective interventions for improving fatigue and quality of life in people with MS, respectively. The findings suggest that exercise is a beneficial treatment option for MS patients, with resistance exercise being particularly effective for fatigue and aerobic exercise for quality of life. The study also notes that the effect of exercise on fatigue is associated with the age of the participants, with younger individuals experiencing greater improvements. The results indicate that exercise can significantly enhance physical and psychological well-being in people with MS. The study was registered with PROSPERO and followed PRISMA guidelines. The research provides evidence to support the clinical recommendation of resistance and aerobic exercise for MS patients to alleviate fatigue and improve quality of life.A systematic review and meta-analysis of 40 randomized controlled trials (RCTs) found that exercise significantly improves balance, walking ability, walking endurance, fatigue, and quality of life in people with multiple sclerosis (MS). Exercise interventions, including aerobic exercise, resistance exercise, and multicomponent training, were effective in reducing fatigue, with resistance exercise being the most effective. Aerobic exercise was most effective in improving quality of life. Younger participants showed greater improvements in fatigue. The study highlights that resistance and aerobic exercise are the most effective interventions for improving fatigue and quality of life in people with MS, respectively. The findings suggest that exercise is a beneficial treatment option for MS patients, with resistance exercise being particularly effective for fatigue and aerobic exercise for quality of life. The study also notes that the effect of exercise on fatigue is associated with the age of the participants, with younger individuals experiencing greater improvements. The results indicate that exercise can significantly enhance physical and psychological well-being in people with MS. The study was registered with PROSPERO and followed PRISMA guidelines. The research provides evidence to support the clinical recommendation of resistance and aerobic exercise for MS patients to alleviate fatigue and improve quality of life.