Background: This study investigated the synergistic effects of yoga training and iron supplementation on Restless Legs Syndrome (RLS) in women with Multiple Sclerosis (MS).Materials and Methods: Forty women with MS and RLS (mean age: 35.6 ± 2 years) participated in this semi-experimental pretest–posttest study. Participants were randomly assigned to four groups (n = 10): control, iron supplementation, yoga training, and combined intervention (yoga plus iron supplementation). RLS severity was assessed using the Restless Legs Syndrome Severity Scale (RLS-SS), and plasma iron levels were measured before and after the intervention. Data were analyzed using 4 × 2 ANOVA, Bonferroni post hoc tests, and paired t-tests in SPSS version 27, with significance set at P < 0.05. Results: The yoga and combined intervention groups showed significant reductions in RLS severity compared with the control and iron supplementation groups (P < 0.001), with the combined group showing the greatest improvement. Body weight decreased significantly in the yoga and combined groups (P < 0.05). Significant differences were also observed among groups in plasma iron levels (P = 0.009). Iron concentrations increased significantly in both the supplementation and combined groups compared with baseline values (P < 0.001). The increase in iron levels in the combined group was significantly greater than in the control group (P = 0.02).Conclusion: Yoga training, especially when combined with iron supplementation, reduced RLS symptoms in women with MS. It also contributed to weight management, while iron supplementation improved iron status. These findings support the use of yoga and iron supplementation as complementary approaches for managing RLS in patients with MS.