In ayurvedic system of traditional medicine, 'medhyarasayanas' — decoction of selected plants are used to improve intellect or cognition abilities. Here, we investigated one such polyherbal formulation (PHF) with ingredients Bacopa monniera, Glycyrrhiza glabra, Valeriana wallechii and Withania somnifera used as a facilitator of learning, retention and recall. We evaluated the safety of this PHF in animal models. We performed acute oral toxicity test using 2000 mg/kg of the formulation as per OECD guideline 423 and observed for toxicity over 14 days. Thereafter, we divided them into four groups of six animals each and administered Normal saline 5 mL/kg, The PHF (Wilmer®) @500, 1000 and 2000 mg/kg in the respective groups over 28 days. We observed no mortality or physical and behavioural abnormalities in both acute and subacute toxicity study. On the 28th day, animals were sacrificed, blood collected for estimation of haematological and biochemical parameters and histopathological examination of organs was performed. There was significant difference (P <0.05) in Mean ± SEM values of haemoglobin, total cholesterol, total protein, ALT, AST, ALP and serum creatinine in the test groups compared to control as analysed by One-way ANOVA followed by Tukey’s multiple comparison test. We observed steatosis and ballooning of hepatocytes, lymphocytic periglomerular infiltrate, eosinophilic hyaline casts and renal tubular coagulation necrosis in histopathology of test groups. Haematologic abnormalities (decrease in haemoglobin concentration), hepatotoxic, nephrotoxic and dyslipidemic effects of the tested PHF were seen in the rats in subacute toxicity study over 28 days, which could be due to the individual plant products, microbial contamination or heavy metals in the formulation in excess of regulatory limits. Hence, it needs further safety evaluation in animals and humans.