Display omitted •Lycium ruthenicum is the plant with the highest anthocyanin content, and the total anthocyanin content reached 24.04 ± 0.07 mg/g.•Purified anthocyanins from L. ruthenicum (LRPA) showed a significant ameliorative effect on atherosclerosis in rats.•The potential mechanism of LRAP to ameliorate atherosclerosis involved modulation of gut microbiota, inflammatory response and lipid metabolism disorders. Lycium ruthenicum is a natural functional food rich in anthocyanins, and anthocyanins have been reported to possess anti-oxidation and hypolipidemic effects. Therefore, ameliorative effect and potential mechanism of purified anthocyanins from L. ruthenicum (LRPA) on atherosclerosis (AS) were investigated. The experimental AS rats were induced by intraperitoneal injection of vitamin-D3 and a high-fat diet for 8 weeks. Oral treatment with LRPA significantly decreased serum TG, TC, LDL-C, TNF-α, and IL-6 levels and atherogenic index while increasing HDL-C concentrations. Histological abnormalities of the aorta, liver and small intestine were obviously alleviated. Moreover, LRPA treatment significantly increased the relative abundance of Bifidobacterium, Lactobacillus, Roseburia, Akkermansia, and Lachnospiraceae_NK4A136_group and decreased Prevotellaceae_NK3B31_group, which was accompanied by upregulating the expression of NF-κB, VCAM-1, CYP7A1, and downregulating SREBP-2. These results indicated LRPA ameliorated AS by reshaping the destructed gut microbiota community and modulation of the signaling pathways of arterial inflammation (NF-κB) and hepatic lipid metabolism (SREBP-2).