Fructose is a commonly used sweetener associated with diets that increase the prevalence of metabolic syndrome (MS). Inhibition of the renin-angiotensin system (RAS) has been consistently demonstrated to reduce MS. However, there has been no direct comparison among different pharmacological modes of inhibiting the RAS concerning their effects on MS. This study investigated the effect of aliskiren, a direct renin inhibitor, versus telmisartan, an angiotensin II-receptor blocker, in the treatment of fructose-induced MS in rats. MS was induced by high fructose (FRC) diet feeding for 12 weeks. Oral administrations of telmisartan (TEL, 5 mg/kg), aliskiren (ALS, 30 mg/kg) or vehicle were started in the last 4 weeks. Results showed that administration of either TEL or ALS with FRC diet equally ameliorated the metabolic parameters (glucose level, oral glucose tolerance test, insulin resistance and serum lipids profile), systolic blood pressure and oxidative stress markers (malondialdehyde, nitric oxide, reduced glutathione levels and catalase activity). Additionally, the effects of TEL and ALS were associated with a decrease in body composition index and attenuation of liver index, serum liver enzyme activities and hepatic expressions of inflammatory and fibrotic markers (tumor necrosis factor-α, nuclear factor kappa-B and transforming growth factor-β) with a significant increase in hepatic glucose transporter-2 and peroxisome proliferator-activated receptors-alpha and gamma expressions. The results suggested that, at indicated dosage, ALS has ameliorative effect equal to that of TEL against FRC-induced metabolic and hepatic disorders; implying that drugs which inhibit the RAS, by different mode of inhibition, profoundly affect fructose-induced MS in rats.