Abstract: Objective: This study aimed to investigate the protective effect and mechanism of yeast extract and curcumin-yeast extract on acute alcoholic liver injury in mice. Methods: The mouse model of acute alcoholic liver injury was established, and the mice were administered with yeast extract and curcumin-yeast extract. Changes in ALT, AST, T-GSH, GSH-Px, and MDA levels were observed in the serum and liver tissue, respectively. Pathological sections of liver tissue were examined to observe the damage. The intestinal flora of mice was analyzed. Results: Compared with the model group, both yeast extract and curcumin-yeast extract reduced the levels of ALT, AST, MDA, TC, and TG, increased the activities of GSH-Px and T-GSH, and alleviated fatty infiltration and inflammatory infiltration of hepatocytes. Curcumin-yeast extract effectively restored the abundance of Acinetobacter, Prevotella, and Ruminococcus, which had been altered by alcohol. The restorative effect was superior to that of the yeast extract group. Conclusion: Yeast extract and curcumin-yeast extract showed significant protective effects against acute alcoholic liver injury in mice. This mechanism may be associated with the regulation of oxidative stress, lipid metabolism, and intestinal flora.