BACKGROUND: The Mediterranean diet is a healthy diet with positive scientific evidence of preventing chronic diseases. Bioactive components support the healthy properties of the Mediterranean diet. Antioxidants and fiber, two components of the Mediterranean diet, are key functional nutrients for healthy eating and nutrition. Wine grape pomace is a rich source of these dietary constituents and may be beneficial for human health. Our hypothesis was that the intake of red wine grape pomace flour (WGPF) prepared from red wine grapes (Cabernet Sauvignon variety) reduced the metabolic syndrome in humans. To evaluate the effect of WGPF on components of metabolic syndrome we design a 16-week longitudinal intervention study. Thirty-eight males, 30-65 years of age, with at least one component of metabolic syndrome, were randomly assigned to either the intervention group (n = 25) or the control group (n = 13). At lunch, the intervention group was given 20 g of WGPF per day, which contained 10 g of dietary fiber, 822 mg of polyphenols and an antioxidant capacity of 7258 ORAC units. Both groups were asked to maintain their regular eating habits and lifestyles. Clinical evaluation, anthropometric measurements and biochemical blood analyses were done at the beginning and the end of the study. RESULTS: WGPF intake significantly decreased systolic and diastolic blood pressure as well as fasting glucose levels. Plasma γ-tocopherol and δ-tocopherol increased and carbonyl group in plasma protein decreased in WGPT group, significantly. No significant effect was observed for waist circumference, HDL cholesterol, triglycerides, total antioxidant capacity and vitamin C in and between groups. The group-dependent magnitude of the differences between the baseline and final postprandial insulin values and γ-tocopherol concentrations was statistically significant. CONCLUSIONS: The consumption of WGPF-rich in fiber and polyphenol antioxidants, as a food supplement in a regular diet improves blood pressure, glycaemia and postprandial insulin. In addition, increased antioxidant defenses and decreased oxidative protein damage indicating attenuation of oxidative stress. WGPF might be a useful food ingredient for health promotion and chronic disease prevention.