ETHNOPHARMACOLOGICAL RELEVANCE: Li-Chong-Xiao-Zhen granules (LCXZG) has the effect of " activate blood and resolve stasis," " soften hardness and dissipate binds " properties, and was widely used in the clinic for decades to treat uterine fibroids and ovarian cancer (OC), which is called "zheng jia" in traditional Chinese medicine. AIM OF THE STUDY: The aim of this study is to identify the active components of LCXZG and elucidate the mechanism of LCXZG in ovarian cancer by combining network pharmacology, metabolomics and proteomics. MATERIAL AND METHODS: The absorbed compounds in serum of LCXZG was identified by liquid chromatography-mass spectrometry. Network pharmacology was used to predict the active components and target genes of LCXZG. The therapy mechanism of LCXZG on OC were determined by establishing a nude mouse xenograft tumor model and using combined metabolomics and proteomics analysis. RESULTS: A total of 218 absorbed compounds in serum of LCXZG were identified by UPLC-MS. Network pharmacology results showed that lipid and atherosclerosis, chemical carcinoma-receptor activation and PI3K-AKT signaling were potential target pathways of LCXZG in the treatment of OC. Further metabolomics and proteomics studies demonstrated that LCXZG altered glycerophospholipid metabolism in ovarian cancer. CONCLUSIONS: This study demonstrated that most of the active Compound of LCXZG are Paeoniflorin, Turanose, Amygdalin and Benzoylpaeoniflorin, which may exert their anti-tumor effects by regulating glycerophospholipid metabolism in ovarian cancer.