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It is well known that allicin has anti-bacterial, anti-oxidation, and anti-inflammatory biological functions. However, there is little information on whether allicin has beneficial effects on ruminants fed a high-grain (HG) diet. This study was conducted to investigate the effects of allicin addition on growth performance, ruminal microbes in different rumen ecological niches (REN), and the rumen epithelial (RE) proteome in fattening goats fed a HG diet. Twenty-four Anhui white goats were randomly allocated to three dietary treatments: control diet (CON, n = 8), high-grain diet (HG, n = 8), and high-grain diet + allicin (HGA, n = 8). After 56 days, blood, rumen fluid (RL), rumen solid (RS), and RE tissue were sampled for further analysis. Compared with the HG diet, the addition of allicin decreased (P < 0.05) the DMI, with no effects (P > 0.05) on daily weight gain and rumen fermentation parameters. The malondialdehyde concentrations were lower (P < 0.05) in the HGA group than in the HG group. The HGA group had a higher activity of glutathione peroxidase in the rumen epithelium than the HG group. The alpha diversity in different REN in the HGA group was higher (P < 0.05) than that in the HG group. Compared to the HG group, the HGA group had higher relative abundances of Lachnospiracea_incertae_sedis, Ruminobacter , and Bifidobacterium (P < 0.05), and lower relative abundances of Methanomassiliicoccus (P < 0.05). The addition of allicin helped mitigate or reverse the differences between the HG diet and the CON diet at the genus level in different RENs. Proteomic analysis of the rumen epithelium showed that proteins involved in cell junction and immune function were downregulated, whereas those involved in oxidative stress and inflammatory reactions were upregulated in the HG group in comparison with the CON group. Compared with the HG group, the addition of allicin increases the abundance of proteins involved in cell junction and immune function and decreases those of proteins involved in oxidative stress and inflammatory reactions. Our findings indicate that the addition of allicin can improve the antioxidant capacity, modify the rumen microbial composition, alleviate the damage to the rumen epithelium cell junction, and protect the rumen epithelium of goats fed a HG diet. • High-grain diets improve productivity but harm the health of ruminants. • The microbiota of the rumen epithelium is less affected by diet. • Allicin has the potential to reshape the rumen microbiota community. • Allicin enhances the immune system without compromising productivity. • Supplementing with allicin can reduce methane-producing bacteria. [ABSTRACT FROM AUTHOR]