Background: Fatigue, depression, and balance impairment are common in patients with multiple sclerosis (MS). Aquatic therapy is an exercise program which is effective in improving the well-being of patients with MS. So, we designed this systematic review to estimate the pooled effects of aquatic therapy on depression, fatigue and balance in subjects with MS. Methods:Two independent researchers did a systematic and comprehensive search of PubMed, Scopus, EMBASE, Web of Science, Google Scholar as well as gray literature, including references of the included studies, and conference abstracts. The search was done on October 31st 2022. We extracted data regarding the total number of participants, first author, publication year, country of origin, mean age, EDSS, and results of fatigue, depression and balance. Results:The first search identified 6403 studies. After deleting duplicates, 3347 studies remained, and 86 full texts were evaluated. Ten studies remained for meta-analysis. The pooled standardized mean difference (SMD) of BBS (after-before) was 0.67 (95% CI 0.19-1.16) (I²=11.6%, P=0.3). The pooled SMD of MFIS (after-before) was -0.4 (95% CI -0.71 to -0.09) (I2=21%, P=0.2). The pooled SMD of FSS (after-before) was -1.13 (95% CI -1.95 to -0.3) (I²=82.5%, P=0.003). The pooled SMD of BDI (after-before) was -1.83 (95% CI -2.31 to -1.35) (I²=30.1%, P=0.2). Conclusion:The results of the present systematic review and meta-analysis show that aquatic therapy is effective for depression, fatigue, and balance improvement in subjects with MS.