BACKGROUND AND OBJECTIVE: Restless legs syndrome/Willis-Ekbom Disease (RLS/WED) is one of the most prevalent sleep disorders. There are contradicting data about the effectiveness of magnesium and vitamin B6 in alleviating the symptoms of this condition. Therefore, this study aimed to assess the efficacy of magnesium and vitamin B6 in alleviating the symptoms of RLS/WED. METHODS: A single-blind study was conducted on individuals with this illness for at least three months. Randomly, 75 patients were assigned into three groups: magnesium, vitamin B6, and placebo. The experimental group received daily doses of 40 mg vitamin B6 or 250 mg magnesium oxide. While others in the control group merely received a placebo. Patients' disease severity and sleep quality were evaluated three times using standard questionnaires (at the beginning of the study, one and two months after therapy). Utilizing SPSS22 software and the ANOVA, t-test, and repeated measure tests, statistical analysis was conducted. RESULTS: The mean and standard deviation of sleep quality and disease severity at the beginning of the trial and throughout the first month following the intervention did not differ statistically between the three groups. In the second month following the intervention, the mean and standard deviation of sleep quality and disease severity were significantly different (P = 0.001). CONCLUSION: Taking magnesium and vitamin B6 supplements can reduce the severity of symptoms of RLS/WED patients and improve their sleep quality.