Limited information from human studies indicates that dietary quercetin supplementation influences blood lipid profiles, glycemic response, and inflammatory status, collectively termed cardiometabolic risks. We tested the hypothesis that quercetin-rich supplementation, derived from onion peel extract, improves cardiometabolic risk components in healthy male smokers in a randomized, double blinded, placebo-controlled parallel design. Randomly assigned subjects were instructed to take either the placebo (n = 43) or 100 mg quercetin capsules each day (n = 49) for 10 weeks. Anthropometric parameters and blood pressure were measured, and blood lipids, glucose, interleukin-6, and soluble vascular cell adhesion molecule-1 (sVCAM-1) were determined at baseline and after 10 weeks of quercetin supplementation. Quercetin-rich supplementation significantly reduced serum concentrations of total cholesterol ( P < 0.05) and LDL-cholesterol ( P < 0.01), whereas these effects were not shown in the placebo group. Furthermore, significant increases were observed in serum concentrations of HDL-cholesterol both in the placebo ( P < 0.005) and quercetin-rich supplementation group ( P < 0.001); however, changes in HDL-cholesterol were significantly greater in subjects receiving quercetin-rich supplementation than the placebo. Both systolic ( P < 0.05) and diastolic blood pressure ( P < 0.01) decreased significantly in the quercetin-rich supplementation group. Glucose concentrations decreased significantly after 10 weeks of quercetin-rich supplementation ( P < 0.05). In contrast, no effects of quercetin-rich supplementation were observed for the inflammatory markers-IL-6 and sVCAM-1. Daily quercetin-rich supplementation from onion peel extract improved blood lipid profiles, glucose, and blood pressure, suggesting a beneficial role for quercetin as a preventive measure against cardiovascular risk.