Individuals with multiple sclerosis (MS) commonly experience fatigue, discomfort, sleep problems, anxiety, and reduced quality of life. Studies have shown that foot reflexology can help relieve these symptoms. The objective of this current study is to systematically review the effects of foot reflexology on patients with MS. We conducted a systematic review of published literature in many databases, including PubMed, EMBASE, and Cochrane Library, from January 1, 2000, to January 27, 2022. With language restrictions, we included randomized controlled trials of foot reflexology interventions for MS that had any clinical or psychological symptom measurements as outcomes. The Cochrane risk-of-bias tool was used to assess evidence quality. Two authors independently screened titles and abstracts. Potential eligible articles were retrieved for full-text review. A third author checked for excluded records. All discrepancies were resolved through a discussion among the 4 reviewing authors. A total of 154 studies were identified; 9 studies with 545 MS patients were included in this review. The most frequently reported findings of foot reflexology intervention in individuals with MS were reductions in fatigue, pain, muscle spasms, stiffness, and psychological symptoms and improvement in bowel and bladder functions and quality of life. The findings suggest that foot reflexology could be a safe and effective modality to reduce the physical and psychological symptoms and also improve the quality of life for individuals with MS; however, well-designed, large-scale trials are required to confirm the effect.