Plant-derived exosome-like nanoparticles (ELNs) contain many bioactive components. Here, Goji-derived ELNs were characterized using transmission electron microscopy and Zeta potential analysis. These ELNs can improve the symptoms of liver injury in alcohol-induced acute liver disease (ALD) in mice, demonstrated by histology of liver sections and serum biomarker levels. Specifically, ELNs elevated the transcriptional level expression of hepatic antioxidant-related genes and colonic barrier-related genes. Additionally, 16S rRNA gene sequencing demonstrated that ELNs modulated gut microbiota by increasing the relative abundance of Akkermansia. Furthermore, metabolomics analysis shows that the protective effects of ELNs on alcohol-damaged intestinal barrier and mucus layer structure may be associated with increased L-asparagine, L-serine, D-glucuronic acid, as well as unsaturated fatty acids like docosahexaenoic acid and eicosapentaenoic acid in the mouse caecum. Overall, these findings suggest that the Goji-derived ELNs can modify gut microbiota and its metabolites, potentially emerging as a novel agent for the treatment of alcohol-induced ALD.