Recent data show that magnesium supplementation decreases systolic and diastolic blood pressure values depending on the blood pressure levels and improves metabolic parameters in cardiovascular disease. In this context, we conducted a prospective, randomized, double-blind study on serum and ionized magnesium, systolic and diastolic blood pressure values, interleukin-6, vitamin D, and metabolic profile in 27 patients (13 male/14 female, age: 60.2±12.5 years) with metabolic syndrome. All patients received 400 mg of oral magnesium supplementation daily. Parameters were measured before and after 6 and 12 weeks of treatment. 27 patients served as controls without additional magnesium treatment (10 male/17 female, age: 64.6±13.2 years). There was no significant change in serum magnesium after 6 and 12 weeks of magnesium supplementation and in controls. Ionized magnesium significantly increased from 0.56±0.05 to up to 0.63±0.08 mmol/L (mean ± SD) (p<0.01). The ionized Ca++/Mg++ ratio was significantly increased at baseline in about 32% of all patients; after 12 weeks of magnesium supplementation, the Ca++/Mg++ ratio decreased significantly from 2.32±0.22 to 2.04±0.24 at the end of the study (mean ± SD, p<0.05). In the magnesium-treated group, there was a significant decrease in systolic and diastolic blood pressure values after 12 weeks (systolic: 134.6±6.8 to 126.3±5.6 mmHg, diastolic: 84.1±3.9 to 79.4±1.6 mmHg) (mean ± SD) (p<0.01). Additional magnesium supplementation decreased interleukin-6 values significantly from 4.94±3.30 to 4.53±6.89 pg/mL after 6 weeks to 3.01±1.32 pg/mL after 12 weeks (mean±SD) (p<0.01). In the control group, interleukin-6 was 3.73±4.36 pg/mL before the start of the supplementation, 4.87±4.35 pg/mL after 6 weeks, and 4.41±3.15 pg/mL after 12 weeks (means ± SD) (n.s.). In patients receiving magnesium supplementation, vitamin D levels significantly improved from 17.93±8.96 to 24.41±10.20 ng/mL (mean±SD) (p<0.05). HbA1c and serum cholesterol values improved under magnesium therapy, but the improvement did not reach significance. For statistical analysis, Mann-Whitney-U-Test was used. Using supplementation with 400 mg magnesium for 12 weeks in patients with metabolic syndrome, ionized magnesium concentrations significantly increased, while serum magnesium did not change significantly. Both systolic and diastolic blood pressure values decreased significantly in the magnesium-treated group. Magnesium supplementation also significantly decreased interleukin-6 levels and increased vitamin D in patients. HbA1c and cholesterol levels improved with magnesium supplementation, but the improvement did not reach significance. The anti-inflammatory effects of magnesium as well as anti-arteriosclerotic effects of magnesium therapy are beneficial for patients with metabolic syndrome at high risk of cardiovascular disease and mortality.