Given the conflicting results about the positive effects of magnesium and L-carnitine and as there is no report concerning concurrent supplementation of magnesium and L-carnitine on migraine prophylaxis, the effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation on migraine indicators were assessed. In this clinical trial, 133 migrainous patients were randomly assigned into three intervention groups: magnesium oxide (500 mg/day), L-carnitine (500 mg/day), and Mg-L-carnitine (500 mg/day magnesium and 500 mg/day L-carnitine), and a control group. After 12 weeks of supplementation, the checklist of migraine indicators including migraine attacks/month, migraine days/month, and headache severity was completed, and serum concentrations of magnesium and L-carnitine were measured by atomic absorption spectrophotometry and enzymatic UV test, respectively. The results showed a significant reduction in all migraine indicators in all studied groups (p < 0.05). The ANOVA results showed a significant reduction in migraine frequency across various supplemented and control groups (p = 0.008). By separating the effects of magnesium supplementation from other confounding factors such as routine treatments using the repeated measures and nested model, it was clarified that magnesium supplementation had a significant effect on all migraine indicators. Oral supplementation with magnesium oxide and L-carnitine and concurrent supplementation of Mg-L-carnitine besides routine treatments could be effective in migraine prophylaxis; however, larger trials are needed to confirm these preliminary findings.