Background: Multiple sclerosis (MS) is a major cause of chronic neurological disability in young adults. An increasing number of controlled studies have assessed the potential rehabilitative effects of new drug-free treatments, complementary to the standard care, including music-based therapy (MBT). Objective: To analyze the evidence for the effectiveness of MBT within the therapeutic approaches to individuals diagnosed with MS. Methods: A systematic review of clinical trials was performed with searches in the following databases: BIOSIS, CINAHL, Cochrane, EBSCO, ERIC, Google Scholar, IBECS, LILACS, LISA (ProQuest), Medline, PEDro, PsycINFO (APA), Psychological & Behavioral, PubMed, SciELO, Scopus, SPORTDiscus and Web of Science. Clinical trials comparing MBT versus conventional therapy/no intervention were included. Results: From the 282 studies identified, 10 trials were selected. Among these, the total sample consisted of 429 individuals: 253 were allocated to the experimental group (MBT) and 176 to the control group (conventional therapies or no intervention). All the studies presented high methodological quality. Modalities of MBT were clustered into four groups: (1) Rhythmic auditory; (2) Playing musical instruments; (3) Dance strategy; and (4) Neurological music therapy. Overall, the studies consistently showed that MBT was better than conventional therapy or no intervention, with regard to gait parameters (double support time and walking speed), fatigue level, fatigability, coordination, dexterity, balance, walking endurance, lower extremity functional strength, emotional status and pain. Regarding mental fatigability and memory, the data were conflicting and the evidence was unclear. Conclusion: MBT is a safe and effective approach for clinical rehabilitation of MS patients that leads to positive results regarding both motor and non-motor functions.