Pomegranates are known to possess anti-hypertensive, anti-atherogenic and cardioprotective effects mainly due to their pleiotropic effects on various cellular pathways, especially those triggered by oxidative stress. The aim of this study was to investigate the effect of natural standardized pomegranate (PE) extract on cardiovascular risk factors in 24 healthy volunteers who participated in a randomized, single-blind placebo-controlled study. There were 12 subjects in the PE group and 12 in the placebo group. Variables were measured at baseline and after 14 and 28 days of supplementation are anthropometry, BP, pulse wave velocity, fat and lean body mass, salivary and urinary cortisol, and cortisone, total phenolics, antioxidant capacity and lipid peroxidation. Urinary total phenolics excretion and antioxidant capacity were significantly increased after 14 and 28 days of PE intake. At day 28, there were also statistically significant decreases in systolic and diastolic blood pressure (BP), pulse wave velocity, body fat and fat mass, as well as an increase in lean body mass. Significant changes in the placebo group were not found. Glucocorticoid levels showed a significant decrease in saliva cortisol at day 28 (morning) in the PE group, and cortisol/cortisone ratio was significantly decreased following 28 days of PE intake at morning, noon, and evening. Urine free cortisol was significantly reduced at day 14. These findings suggest that pomegranate extract intake may improve antioxidant and oxidative stress status and play a beneficial role in the attenuation of some cardiovascular risk factors. Future studies should concentrate on overweight and older people.