The objective of this study was to investigate the effect of sesame oil in hypertensive diabetics medicated with atenolol (beta-blocker) and glibenclamide (sulfonylurea). This open label trial with two intervention periods comprised 22 male and 18 female patients, 45-65 years old, with mild to moderate hypertension and diabetes. Sesame oil (Idhayam Gingelly (TM) oil, V.V.V. & Sons, Virudhunagar, Tamilnadu, India) was supplied to the patients, who were instructed to use it in place of other cooking oils for 45 days. Blood pressure (BP), anthropometric measurements, plasma glucose, glycated hemoglobin (HbA(1c)), lipid profiles [total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol, and triglycerides (TG)], lipid peroxidation [thiobarbituric acid-reactive substances (TBARS)], electrolytes (sodium, potassium, and chloride), and enzymic (superoxide dismutase, glutathione peroxidase, and catalase) and nonenzymic (vitamin C, vitamin E, beta-carotene, and reduced glutathione) antioxidants were measured at baseline and after 45 days of sesame oil substitution. The same patients were then switched over to other oils like palm or groundnut oils as their regular oils at random for another 45 days, and the investigations were carried out again at the end. Systolic and diastolic BP decreased remarkably. When oil substitution was withdrawn, BP values rose again. Body weight, body mass index, girth of waist, girth of hip, and waist:hip ratio were reduced upon substitution of sesame oil. Plasma glucose, HbA(1c), TC, LDL-C, and TG were decreased. TBARS level was reduced, while the activities of enzymic and the levels of nonenzymic antioxidants were increased. Plasma sodium levels were reduced, while potassium levels were elevated. These results indicate that substitution of sesame oil as the sole edible oil has an additive effect in further lowering BP and plasma glucose in hypertensive diabetics.