Health and wellbeing are significantly impaired by alcoholic liver disease (ALD), and although some lactic acid bacteria strains have been shown previously to relieve ALD symptoms, the mechanisms behind these effects are still unclear. Here, the Lieber-DeCarli liquid diet containing alcohol was fed to C57BL/6J mice for 6 weeks to build a chronic alcoholic liver lesion model to study the protective effects and possible mechanisms of Lactobacillus mixture ( KLDS1.0344 and KLDS1.0901). The results showed that Lactobacillus mixture improved intestinal epithelial permeability and reduced the serum lipopolysaccharide (LPS) levels. Furthermore, Lactobacillus mixture inhibited liver lipid accumulation, oxidative stress, and inflammation by regulating AMPK, Nrf-2, and TLR4/NF-κB pathways. Importantly, the Lactobacillus mixture modulated the gut microbiota, resulting in increased short-chain fatty acid (SCFA) producers and decreased Gram-negative bacteria. Taken together, these findings indicated that the Lactobacillus mixture could positively regulate the gut microbiota, causing increased levels of SCFAs, which inhibited alcohol-induced liver lipid accumulation and oxidative stress through the gut-liver axis. Moreover, following administration of the Lactobacillus mixture, the improvement of intestinal epithelial permeability and the reduction of Gram-negative bacteria led to the decrease of LPS entering the portal vein, thereby inhibiting alcohol-induced liver inflammation.