Aim To investigate the new potential mechanisms of carotid atherosclerosis pathogenesis and explore the potential targets and pathways of berberine intervention in carotid atherosclerosis by bioinformatic research. Methods The study searched the Gene Expression Omnibus database of the National Center for Biotechnology Information (NCBI)and obtained the GSE28829 datasets of carotid atherosclerosis plaque gene expression microarray, screened the sample differentially expressed gene data for enrichment analysis. The potential targets of berberine were searched and obtained to be intersected with the differentially expressed genes of carotid atherosclerosis in order to obtain the potential targets of berberine intervention in carotid atherosclerosis. Enrichment analysis was performed and the core targets were screened. Results A total of 174 differentially expressed genes in carotid atherosclerosis were screened, involving chemokines, nuclear factor kappa B, Toll-like receptors, fatty acid degradation and other signaling pathways. Five potential targets of berberine in carotid atherosclerosis were screened, involving fluid shear and atherosclerosis, interleukin-17, tumor necrosis factor and other signaling pathways. Monocyte chemoattractant protein-1(MCP-1/CCL2), heme oxygenase 1(HO-1/HMOX1) and matrix metalloproteinase-9(MMP-9) were identified as the core targets of berberine intervening carotid atherosclerosis by topology and enrichment analysis. Conclusions Differentially expressed genes in carotid atherosclerosis are mainly enriched in signaling pathways such as inflammatory response and lipid metabolism; berberine may intervene in carotid atherosclerosis by mediating targets such as CCL2, HMOX1, MMP-9, and regulating fluid shear and atherosclerosis, interleukin-17, and tumor necrosis factor and other signaling pathways.