Abstract: Purpose: This study aimed to examine the immunomodulatory effects of β-glucan on the compromised intestinal barrier caused by alcohol exposure and to elucidate the underlying mechanisms. Methodology: A murine model of alcohol consumption was used to assess the impact of β-glucan on biochemical parameters in serum and intestinal tissues, as well as on the pathological morphology of intestinal tissues. Mice were administered β-glucan through gavage at varying concentrations (low dose, 0.1 g/mL; high dose, 0.2 g/mL) once daily. Results: Compared with the levels in model group, mice receiving both low and high doses of β-glucan exhibited a significant increase in the levels of secretory immunoglobulin A and interleukin (IL)-10, with a notable decrease in IL-6 (P<0.05 or P<0.01). In addition, β-glucan treatment significantly modulated Enterobacter levels in both tissues and cecal contents, while downregulating Lipopolysaccharide and Diamine Oxidase levels (P<0.05 or P<0.01). Furthermore, β-glucan markedly ameliorated the pathological alterations in intestinal tissues, preserved the structural integrity and functionality of goblet cells, and inhibited apoptosis. It also facilitated the regulatory expression of intestinal barrier proteins zonula occludens-1 and claudin-1, while suppressing IL-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway activation, thereby protecting the intestinal tract. Conclusion: β-glucan exerts a protective effect on the alcohol-damaged intestinal barrier, effectively enhancing intestinal barrier function in mice, regulating Enterobacter levels, and inhibiting IL-6/STAT3 signaling pathway activation and apoptosis.