Background and Aim. Cardiovascular risk is increased in women with menopause and metabolic syndrome. Aim of this study was to test the effect of a new supplement formula, combining cocoa polyphenols, myo-inositol, and soy isoflavones, on some biomarkers of cardiovascular risk in postmenopausal women with metabolic syndrome.Methods and Results. A total of 60 women were enrolled and randomly assigned (n=30per group) to receive the supplement (NRT: 30 mg of cocoa polyphenols, 80 mg of soy isoflavones, and 2 gr of myo-inositol), or placebo for 6 months. The study protocol included three visits (baseline, 6, and 12 months) for the evaluation of glucose, triglycerides, and HDL-cholesterol (HDL-C), adiponectin, visfatin, resistin, and bone-specific alkaline phosphatase (bone-ALP). At 6 months, a significant difference between NRT and placebo was found for glucose (96±7versus108±10 mg/dL), triglycerides (145±14versus165±18 mg/dL), visfatin (2.8±0.8versus3.7±1.1 ng/mL), resistin (27±7versus32±8 µg/L), and b-ALP (19±7versus15±5 µg/mL). No difference in HDL-C concentrations nor in adiponectin levels between groups was reported at 6 months.Conclusions.The supplement used in this study improves most of the biomarkers linked to metabolic syndrome. This Trial is registered withNCT01400724.