Vine tea is documented in ancient Chinese books as having the function of promoting blood circulation. However, its effects and mechanisms remain unclear. The aim of this study was to comprehensively investigate the protective potential and mechanisms of vine tea in high-fat diet rat through a combination of in vivo and in vitro experiments. The efficacy of vine tea was evaluated using a high-fat diet rat model and an oxidized low-density lipoprotein-treated cell model, with physiological and biochemical indicators measured in rat serum and cell supernatants. Transcriptomics was utilized to investigate alterations mRNA expression following the administration of dihydromyricetin in cell model. Metabolomics and 16S rRNA sequencing was employed to examine changes in metabolites in the serum and changes in gut microbiota of high-fat diet rats after administering vine tea extract. Vine tea extract and dihydromyricetin can reduce elevated levels of lipids, including total cholesterol and triglycerides, following modeling. Transcriptomic data indicate that dihydromyricetin exerts its effects by regulating ferroptosis signaling pathways. Metabolomic analysis demonstrates that the administration of vine tea extract influences the vitamin K cycle and glutathione, thereby alleviating the progression of ferroptosis. Additionally, 16S rRNA sequencing reveals that vine tea extract increases Lactobacillaceae in the gut microbiota, which subsequently affects the levels of lysophosphatidylcholine, a major phospholipid component of oxidized low-density lipoprotein in serum. Our results indicate that vine tea can regulate ferroptosis signaling pathways and increase Lactobacillaceae in the gut microbiota, thereby exhibiting cardiovascular protective effects in high-fat diet rats.