Lithocarpus polystachyus Rehd. or Lithocarpus litseifolius (Hance) Chun., a natural functional food highly rich in trilobatin and phlorizin, is named “sweet tea” (ST) in the Chinese folk. The present study aims to explore the protective effects of ST and trilobatin against alcoholic liver injury and its potential mechanisms. Firstly, KM mice were given alcohol to establish an alcohol exposure model, and ST and trilobatin were administered for 3 weeks. The results of the animal experiment manifest that ST and trilobatin probably enhanced alcohol metabolism and inhibited oxidative stress activation to exhibit their hepatoprotective properties. Besides, the outcomes of 16S rRNA Gene Sequencing Analysis provided the first evidence that trilobatin enriched the beneficial microbiota abundance and decreased the bacterial community diversity and potential detrimental bacteria, thus modulating the gut microbiota and maintaining the integrity of barrier function. Overall, ST and trilobatin could alleviate alcohol-induced acute liver damage in mice via modulating gut microbiome. These findings laid the foundation for the further the development and application of ST and trilobatin in functional foods and nutraceutical supplements for preventing liver injury.