Introduction / Rationale: Multiple Sclerosis (MS) is a chronic neurodegenerative disease that leads to impaired body functions including lower extremities (LE). Occupational therapy for MS may utilized orthosis to alleviate the impact of MS symptoms and improve LE function. Objectives: To summarize and synthesize existing evidence on the effectiveness of orthosis on LE functions in individuals with MS. Methods / Approach: This PROSPERO registered systematic review followed the PRISMA guidelines. The systematic search included both electronic and manual searches using databases such as the Academic Search Ultimate, CINAHL Plus, Medline complete, PubMed, and Google Scholar. The eligibility criteria included peer-reviewed studies published in English that investigated the effectiveness of orthosis on LE functions in adults with MS. Search terms and phrases represented the categories of Multiple Sclerosis and Orthosis. Quality assessment and level of evidence were assessed for all included studies. Results / Practice Implications: A total of 12 studies were included in this systematic review. Including a total of 228 adult participants with MS. Outcomes included balance performance, gait, muscle power, and sensation. Static and dynamic orthoses were effective in improving balance and muscle strength. There were conflicting findings on the effectiveness of orthosis on gait performance, while there were no effects on planter sensation after using orthosis. Conclusion / Contribution to the occupational therapy profession: orthoses are effective in improving specific body functions in LE like balance and muscle strengths. There is a need to further investigate orthoses effectiveness on activities and participation like functional mobility and gait.