Abstract: To explore the effect of Astragalus membranaceus, a traditional Chinese medicine, on metabolic homeostasis of heart, brain and blood in mice, and to elucidate the cardio-cerebrovascular protective mechanisms of AR from the perspective of metabolic regulation. Thirteen ICR male mice were randomly divided into two groups which were intragastrically administered with ultrapure water and aqueous extract of Astragalus membranaceus for 10 consecutive days, respectively. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) were used to comprehensively characterize the metabolic profiles of serum, heart and brain tissues. Multivariate statistical analysis combined with nonparametric tests were applied to screen and identify different metabolites, and then the related metabolic pathways were uncovered. Multivariate statistical analysis showed that the metabolic profiles of serum, heart, and brain tissues of mice after Astragalus membranaceus intervention significantly changed compared with the control group. A total of 15, 19, and 17 metabolites were identified in serum, heart, and brain tissues, respectively, among which palmitic acid and LysoPC (20∶3) were screened out from all types of biological samples. The results of metabolic pathway enrichment analysis showed that amino acid metabolism, phospholipid metabolism, fatty acid metabolism and tricarboxylic acid cycle were significantly affected. Astragalus membranaceus may protect the cardio-cerebrovascular system by regulating the metabolic homeostasis of amino acids, lipids and energy.