Abstract Background: Liver fibrosis is a reversible pathological process, and its prevention and treatment are of great significance to patients with chronic liver disease. This study combined 16S rRNA analysis of gut microbiota and plasma metabolomics to explore the mechanism of curcumol’s effect on liver fibrosis in mice. The results will help to clarify the relationship between the gut microbiota and metabolites in the process of liver fibrosis. Results: Molecular biological testing found that curcumol could significantly improve the pathological changes of liver tissue and inhibit the occurrence of liver inflammation. Intestinal flora testing found that curcumol could significantly change the abundances of Veillonellaceae, Prerotella_oulorum, and Alistipes_finegoldii. Metabolomics analysis found that curcumol’s anti-hepatic fibrosis effect may be related to its regulation of arachidonic acid metabolism. Correlation analysis suggested that curcumol regulated the abundances of Bacteroidota and Bacteroides and participated in the metabolism of Prostaglandin B2. Conclusions: When liver fibrosis occurs, the intestinal flora and metabolic network will be altered. The effect of curcumol on liver fibrosis may be related to its regulation of intestinal flora and the resulting interference with metabolic pathways, thereby regulating liver inflammation.