Background: Metabolic syndrome (MetS) and its relationship with cognitive impairment has been the subject of extensive research. Purpose: This study was designed to determine the effect of MetS on cognitive function, and the possibility of modulating this effect by exenatide, metformin and folic acid. Materials and Methods: 30 adult male albino rats were divided in 5 groups. Group (I): received a standard rat chow, group (II): none treated rats with MetS fed with 60% fructose added to the standard rat chow, group (III): rats with MetS treated with exenatide, group (IV): rats with MetS treated with metformin, group (V): rats with MetS treated with folic acid. At the end of the experiment, fasting blood glucose, fasting plasma insulin, HOMA-IR index, serum triglyceride, HDL-C, dopamine and BDNF levels in brain tissue were measured and cognitive performance was assessed by Morris water maze (MWM) test. Results: rats with MetS showed increased levels of fasting blood glucose, fasting plasma insulin, HOMA-IR index, arterial blood pressure, serum triglycerides, decreased HDL-C, dopamine and BDNF and showed memory impairment in MWM test. All treated groups resulted in decrease in fasting blood glucose, fasting plasma insulin, HOMA-IR index, arterial blood pressure, and serum triglycerides and increase in HDL-C, dopamine and BDNF as well as improvement in MWM test. Conclusion: MetS was associated with cognitive impairment. Exenatide, metformin and folic acid improved cognitive function in addition to improvement of metabolic parameters.