Ziziphora clinopodioides Lam. (Lamiaceae) is traditionally used in Uighur's medicine for the treatment of hypertension. Our study determined and evaluated the bioactive compounds by performing an activity-guided fractionation of a hydroalcoholic extract of the whole plant, using an in vitro model of rat isolated thoracic aortic rings. Seven compounds were identified as active principles: acacetin, apigenin, chrysin, thymonin, acetovanillone, 4-hydroxyacetophenone and ethyl 4-coumarate. Apigenin, chrysin and ethyl 4-coumarate were found to be the most effective. Our results provide the first evidence that the vasodilation induced by Z. clinopodioides Lam. is mediated, at least in part, by phenolic components.