Evidence supports positive effects of exercise on mental health outcomes among people with Multiple Sclerosis (PwMS). However, non-traditional exercise modes like Pilates remain understudied. PURPOSE: This randomized controlled trial investigated the effects of eight weeks of twice weekly home-based Pilates training compared to delayed-start wait-list condition on symptoms of anxiety, depression, and fatigue among 54 females (46.7±9.6 y) with physician diagnosed MS (Patient Determined Disease Steps score <3), no previous Pilates experience, and no other significant physical or psychiatric condition. METHODS: After providing informed consent, participants were randomised to twice weekly home-based Pilates sessions guided by a DVD or delayed-start wait-list. Well-validated questionnaires assessed symptoms of anxiety, depression, and fatigue at baseline, and weeks two, four, six and eight of the intervention. Compliance was documented in weekly exercise diaries and followed-up by a phone call from the first author. RM-ANOVA examined between-group differences across time. Hedges’ d quantified the magnitude of differences in outcome change for home-based Pilates compared to delayed-start wait-list. RESULTS: Group X time interactions were significant for depressive symptoms (F_(4,50)=3.21, p≤0.02), physical symptoms of fatigue (F_(4,50)=3.45, p≤0.01), cognitive symptoms of fatigue (F_(4,50)=3.08, p≤0.02), psychosocial symptoms of fatigue (F_(4,50)=3.51, p≤0.009), and total fatigue (F_(4,50)=3.82, p≤0.007). Compared to wait-list, home-based Pilates significantly reduced (all p≤0.041) depressive symptoms at weeks 6 (d=0.39), and 8 (d=0.69), physical symptoms of fatigue at weeks 2 (d=0.41),4 (d=0.24), 6 (d=0.57), and 8 (d=0.87), cognitive symptoms of fatigue at weeks 4 (d=0.39), 6 (d=0.32), and 8 (d=0.60), psychosocial symptoms of fatigue at weeks 2 (d=0.51),4 (d=0.48), 6 (d=0.58), and 8 (d=0.69), and total fatigue at weeks 2 (d=0.23),4 (d=0.37), 6 (d=0.53), and 8 (d=0.84). CONCLUSION: Home-based Pilates improved mental health outcomes among females with MS, including moderate magnitude reductions in depressive and fatigue symptoms. These findings support the potential of home-based Pilates to improve several mental health symptoms prevalent among PwMS.