Abstract:[Background] Dihydromyricetin (DMY) is a major flavonoid compound in Vine tea (Ampelopsis grossedentata), which has antioxidant, anti-inflammatory, and other effects. Its medicinal value has attracted extensive attention, but its biological activity in vivo and catabolic mechanism in intestine are still unclear. [Objective] To explore the effects of dihydromyricetin on serum antioxidant capacity and intestinal microbial diversity of mice under antibiotic stress. [Methods] The experimental mice were divided into a control group, an antibiotic group, and an antibiotic+dihydromyricetin group. The antioxidant indexes in the serum of mice in each group were detected. The differences of intestinal microbial diversity between groups were analyzed by high-throughput sequencing. The relative abundance differences between specific bacterial groups were verified by real time fluorescence quantitative polymerase chain reaction (RT-qPCR). [Results] Dihydromyricetin significantly increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) in the serum of antibiotic stressed mice (P<0.05), significantly decreased the content of malondialdehyde (MDA) (P<0.05), catalyzed the synthesis of nitric oxide (NO), and significantly increased the total antioxidant capacity of mice. There were significant differences in the composition and structure of intestinal microorganisms between the antibiotic+dihydromyricetin group and the antibiotic group. Dihydromyricetin improved the composition of intestinal flora in mice by regulating the abundance ratio of Firmicutes and Bacteroidetes, promoting the proliferation of bacteria such as Lactobacillus and Clostridium, and inhibiting the proliferation of Enterobacteriaceae, so as to increase the relative abundance of beneficial bacteria related to intestinal catabolism such as Lactobacillus and Clostridium in the intestinal tract of mice. [Conclusion] Dihydromyricetin can change the structure of intestinal flora. Some probiotics are heavily involved in its metabolic process and produce beneficial metabolites to improve the antioxidant capacity of the body and maintain intestinal health. Negative effects of antibiotics on the intestinal tract of mice are thus reduced. These findings provide a theoretical basis for the study of the function and catabolic mechanism of dihydromyricetin.