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Cereal vinegar sediment (CVS), a byproduct of traditional vinegar fermentation, has been regarded as a health-promoting product. However, its role in genetically induced hyperlipidemia remains unclear. This study systematically evaluated the effects of Dade-CVS (DD-CVS) and Hengshun-CVS (HS-CVS) on apolipoprotein-E-deficient (Apoe^−/−) mice. Both CVS varieties significantly improve certain serological parameters of Apoe^−/− mice, although the overall impact on serum indicators remains limited. Nevertheless, 16S rRNA sequencing revealed that CVS treatment reshaped gut microbial communities to a notable extent. Compared with the Apoe^−/− mice, the DD-CVS treatment significantly increased the relative abundance of Dubosiella while reducing the genus Desulfovibrio, whereas the HS-CVS treatment inhibited the growth of Bifidobacterium and Akkermansia. The pathways predicted in the KO-DD group included vitamin, amino acid, and energy metabolism, while HS-CVS treatment was associated with bile acid biosynthesis and energy pathways. Metabolomic analysis showed that several key metabolites, including N1-acetylspermidine, succinic acid, and 25-hydroxycholesterol, were significantly altered following CVS supplementation. Correlation analysis revealed significant associations between serum indicators and these metabolites. Alistipes, Enterorhabdus, and Romboutsia were also correlated with serum indicators. Overall, these findings indicate that CVS primarily modulated the gut microbiota–metabolite axis and partial lipid modulation in hyperlipidemic mice. The study provides a reference for studies on the beneficial functions of CVS in hyperlipidemia. Full article