The objective of this study was to investigate the possible mode(s) of action for the medicinal use of Orchis mascula (OM) (family Orchidaceae) in hypertension and dyslipidemia. In spontaneously hypertensive rats (SHRs), OM significantly (P<0.05) reduced systolic blood pressure to 174.2±9.63 vs. 203.4±7.13mmHg (mean±s.e.m.; n=7-10) and improved endothelial dysfunction by increasing acetylcholine-induced relaxation. In normotensive anesthetized rats, the crude extract of OM (Om.Cr) at 10 and 30 mg kg-1 caused a dose-dependent attenuation of mean arterial pressure. OM also decreased serum triglycerides to 29.28±6.99 vs. 93.84±5.7 mg per 100 ml (P<0.001), low-density lipoprotein-cholesterol to 5.99±1.27 vs. 21.9±3.5 mg per 100 ml (P<0.05) and atherogenic index to 0.096±0.017 vs. 0.36±0.08 mg per 100 ml (P<0.05). OM significantly reduced lipid levels in tyloxapol and high fat diet-induced hyperlipidemia. In a second model, OM also reduced gain in body weight with a reduction in daily diet consumption. In isolated rabbit aorta, Om.Cr caused concentration-dependent relaxation of both phenylephrine and high K+ (80 mM)-induced contractions and a rightward shift of the calcium concentration-response curves similar to the effect seen with verapamil. In conclusion, OM shows antihypertensive and endothelial-modulating effects mediated through multiple pathways that include direct vasodilation by calcium channel blockade and reduction of plasma lipids by inhibition of biosynthesis, absorption and secretion. This study rationalizes the medicinal use of OM in hypertension and dyslipidemia. However, further studies are required to identify the active constituents of this plant.