Pre-clinical studies suggest that sesame and its lignans induce beneficial changes in risk factors related to cardiovascular disease. This study was designed to investigate the effects of sesame on reducing serum lipids and enhancing antioxidant capacity in 38 hyperlipidemic patients who were divided into two groups randomly. For all individuals along the 60 days of study period, the same drug treatments were considered. Intervention group patients were supposed to eat 40 g white sesame seeds daily, and instead of these calories, 240 kcal was removed from their diet. Anthropometric measurements including height, weight and body mass index (BMI) were measured. We assessed lipid profile and oxidative stress indicators such as glutathione peroxidase (GPX), superoxide dismutase (SOD) and thiobarbituric acid reactive substances (TBARS) before and after the intervention. Significant differences among and between the groups were determined by independent t-test and paired sample t-test using 13th version of statistical package for the social sciences. The results showed that the diet with sesame significantly decreased the levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and TC/HDL-C ratio. Lipid peroxidation (TBARS) decreased while the activities of GPX and SOD were increased. There were no significant changes in anthropometric indexes such as weight and BMI after consumption of sesame. The results suggested that sesame seed supplementation decreased serum TC, LDL-C and lipid peroxidation, and increased antioxidant status in hyperlipidemic patients.