The present investigation was aimed at providing the pharmacological basis for the medicinal use of a polyherbal formulation (POL-10) in hypertension and dyslipidemia. In spontaneously hypertensive rats, POL-10 significantly (p<0.05) reduced blood pressure to 183.2+/-2.97 vs 198.1+/-5.2 mmHg (Mean+/-S.E.M; n=7-10), improved endothelial dysfunction (p<0.01) by increasing acetylcholine-induced relaxation up to 46.0+/-6.7% vs 24.6+/-3.8% (n=5-10) and decreased serum triglycerides (TG) to 54.5+/-3.3 vs. 93.84+/-5.7 mg/dl (p<0.001). In high fat diet-induced hypercholesterolemia, POL-10 caused reduction in total cholesterol (TC), low density lipoproteins (LDL) levels and the atherogic index (TC-HDL/HDL). It decreased TG levels in tyloxapol-induced hyperlipidemia and increased high-density lipoprotein cholesterol (HDL-C) and reduced atherogenic index in normotensive rats. It exhibited strong antioxidant activity in different in vitro assays. In isolated smooth muscle preparation, POL-10 exhibited calcium channel blocking (CCB) activity by inhibition of high K(+)- induced contractions and rightward shift of Ca(++) concentration-response curves similar to that of verapamil. In conclusion, these findings rationalize the medicinal use of POL-10 in cardiovascular disorders which are mediated through multiple pathways such as, antioxidant, CCB, inhibition of lipid biosynthesis and absorption.