Ethnopharmacological relevance: For more than ten scores years, the leaves and fruits of Nitraria sibirica have been used as a natural remedy for indigestion, irregular manes, and hypertension in the Middle East and Central Asia, especially, are recommended for hypertension treatment in the northwest region, China. Aim of the study: we aimed to support the traditional usage of N. sibirica leaves as pharmaceuticals or dietary supplements in treatment of hypertension by investigating their chemical constituents and anti-hypertensive activity. Methods: We identified the chemical composition of N. sibirica leaves ethanolic purified extract (NSL-EPE) using UHPLC-quadrupole-orbitrap-MS, and quantified the main chemical constituents by an analytical method established and validated. We also evaluated anti-hypertensive activity of NSL-EPE using spontaneously hypertensive rats (SHR): blood pressure was measured weekly by non-invasive blood pressure (NIBP) measurements; hemodynamic parameters, biochemical and clinical chemistry variables in plasma, serum and kidney tissue were measured after 10 weeks of treatment with NSL-EPE as well. Results: UHPLC-quadrupole-orbitrap-MS analysis identified 52 compounds, of which 40 compounds were reported for the first time in N. sibirica. 11 phenolic compounds further quantitatively analyzed, among which the most abundant compound was found to be clovin (8.8%). Systolic blood pressure decreased progressively from the second treatment week compared to that in non-treated SHRs. The plasma endothelin, aldosterone, angiotensin II levels were significantly increased, while the level of NOx was significantly decreased; glutathione to oxidized glutathione ratio, superoxide dismutase and total catalase levels in the kidney tissue were markedly accelerated, while malondialdehyde level was significantly reduced in NSL-EPE treated SHRs. Moreover, the serum cholesterol, triglyceride, blood uria nitrogen and creatinine were attenuated in NSL-EPE treated SHRs (P < 0.05), but in sharp contrast to those values in the water-treated SHRs. Conclusion: This study screened out leading compounds from N. sibirica and offered a new understanding of the antihypertensive properties of N. sibirica leaves, by which inhibit oxidative stress-induced endothelial dysfunction and improve lipid profiles.