The purpose of this study was to investigate the effect of physical telerehabilitation on the quality of life (QOL) in patients with multiple sclerosis (PwMS) in a randomized controlled trial. PwMS in both groups received home-based individualized exercise plan based on their physical therapy exam. PwMS in the intervention group were guided by a telerehabilitation system in following their exercise program on a daily basis whereas PwMS in the control group received periodic newsletters. Disease-specific QOL was assessed by MSQOL-54 survey at the baseline and the end of 3-month rehabilitation program. Among the MSQOL sub-scales, the mean sub-score values for pain and cognitive function in control and intervention groups were significantly different as demonstrated by one-way ANOVA (pain: F = 4.301, p = 0.044, cognitive function: F = 5.053, p = 0.030). Our results demonstrated positive effects of physical telerehabilitation on MS symptoms and QOL. Development of further approaches promoting continuous participation in telerehabilitation in PwMS is warranted.