The Pilates Method is a rehabilitation tool with verified benefits in pain management, physical function, and quality of life in many different physiotherapy areas. It could be beneficial for patients with multiple sclerosis (pwMS). The aim of the study was to summarize current evidence for the effectiveness of Pilates in pwMS. A comprehensive search of Cinahl, Scopus, Web of Science, PEDro, and PubMed (including PubMed Central and Medline) was conducted to examine randomized controlled trials (RCT) that included Pilates intervention in multiple sclerosis. The PEDro scale and the Cochrane risk-of-bias tool, RoB-2, were used to evaluate risk of bias for RCT. Twenty RCT (999 patients) were included. Ten were of good quality (PEDro), and seven had low risk of bias (RoB-2). Pilates improves balance, gait, physical-functional conditions (muscular strength, core stability, aerobic capacity, and body composition), and cognitive functions. Fatigue, quality of life, and psychological function did not show clear improvement. There was good adherence to Pilates intervention (average adherence ≥ 80%). Cumulative data suggest that Pilates can be a rehabilitation tool for pwMS. High adherence and few adverse effects were reported. Future research is needed to develop clinical protocols that could maximize therapeutic effects of Pilates for pwMS.