Multiple sclerosis (MS) is a chronic neurological disease which affects young adults at a time of maximum personal, professional and social growth. Recent guidelines on physical activity have established that exercise is an essential component of the clinical management of people with MS with mild or moderate degree of disability. The main purpose of this study was to test the feasibility and the effects of two different 40-week structured physical exercise interventions (a supervised high intensity interval training plus home exercise program and a self-applied home-based exercise program) on clinical evolution, psychological wellbeing, quality of life, fatigue, cardiorespiratory fitness, strength and balance of people with MS. Twenty-nine participants with relapsing-remitting MS (RRMS) participated in this study. All of them were fully ambulatory and with minimal disability (Expanded Disability Status Scale <3), for at least the last six months. Participants selected to be part of a combined face-to-face plus home exercise group (CFTFG; n = 8); a self-applied home-based exercise group (HG; n = 11) or a control group (CG; n = 10). A total of 23 participants completed the protocol (79.3%), of which 8 participants (100%) from the CFTFG, 7 (63.6%) from the HG and 8 (80%) from the CG. During the first 20-weeks of training, adherence from the CFTFG reached 77.5% and from the HG reached 50 %. During the second 20-weeks of training, adherence from the CFTFG reached 62.5% and from the HG reached 45.4%. After 20-weeks of training, a significant improvement in the absolute VO