BACKGROUND: This study employs network pharmacology and molecular docking methods in conjunction with animal experimentation to elucidate the underlying mechanism by which the combination of salvianolic phenolic acids and hawthorn triterpenic acids (SHC) exerts its therapeutic effect on carotid atherosclerosis (AS) in ApoE METHODS: A network pharmacology research approach was used to predict potential core targets for SHC intervention in atherosclerosis. The predictions were subsequently validated through the implementation of animal RESULTS: A total of 23 core compounds were identified in SHC, and 55 core targets of SHC were screened as potential targets for intervention in AS. The results of the enrichment analysis indicated that the principal mechanisms through which SHC exerts its effects in AS are associated with lipid metabolism and the PI3K-Akt and MAPK pathways. The results from animal experiments demonstrated that atorvastatin and SHC markedly reduced the area of carotid plaque and downregulated the levels of TC and LDL-C in ApoE CONCLUSION: It is hypothesized that SHC may reduce lipid deposition and plaque formation in AS by regulating blood lipids, a process that may be closely linked to the inhibition of inflammatory regulator expression, including NF-κB and p38-MAPK.