Multiple sclerosis (MS) is a progressive disease associated with the destruction of the myelin sheath of the central nervous system. The most common problems in these patients are muscle fatigue and balance disorders. Therefore, the aim of this study was to investigate the effect of 12-week yoga practice on fatigue and balance in male and female patients with MS. In this study, 22 men and women with MS, members of the Fars MS Association, were randomly divided into equally experimental (yoga exercises) and control groups. Muscle fatigue was measured by electromyography and balance index was measured by leaf balance test before and after yoga exercises. Data were analyzed using independent and paired t-tests. The results showed that after 12-week yoga practice, it had a significant effect on the amount of electromyography signal from muscle fatigue. Moreover, the results related to balance indicated an improvement in balance indices after 12 weeks of balance exercises in the experimental group compared to the control group. According to the results, this exercise method can be used to improve muscle fatigue and balance in these patients.