Background: S-methyl cysteine (SMC) is a hydrophilic cysteine-containing compound naturally found in garlic and onion. The purpose of the present study was to investigate the protective effect of SMC on oxidative stress, inflammation and insulin resistance in an experiment of metabolic syndrome.Methods: Male Wistar rats were divided into five groups (6 rats in each group), namely; control, control+S-methyl cysteine (SMC), high fructose diet (HFD), HFD+SMC and HFD+metformin. The 60% fructose used for 8 weeks and SMC in the dose of 100 mg/kg bw/day/rat was used in the study. The fasting glucose, insulin, insulin resistance, and tumor necrosis factor alpha and erythrocyte enzymatic antioxidants were measured.Results: Increased levels of plasma glucose, insulin, malondialdehyde, tumor necrosis factor-alpha, and insulin resistance and decreased levels of glutathione, glutathione peroxidase, and catalase were found in rats on a high fructose diet. Oral administration of SMC (100 mg/kg bw/day/rat) for 60 days resulted in significant attenuation of plasma glucose, insulin, tumor necrosis factor–alpha, insulin resistance and improved antioxidant enzyme activities.Conclusion: Oral treatment of SMC is effective in improving insulin resistance while attenuating metabolic syndrome, inflammation, and oxidative stress in male rats fed with fructose rich diet.