The natural xanthone derivative mangiferin (MG) has recently been identified as possessing hepatoprotective potential. Yet, its natural form suffers from low bioavailability, and until now, the effects of a more bioavailable mangiferin sodium salt derivative (MG-Na) on alcohol-induced liver damage had not been evaluated. In this study, we administered MG-Na to rats during alcohol consumption and conducted pharmacological and metabolomic research to assess its impact on liver metabolism, oxidative stress, and inflammation. Our results show that MG-Na effectively mitigated alcohol-induced liver injury, diminishing oxidative stress, inflammation and lipid accumulation. These outcomes may be attributed to the modulation of alcohol oxidation metabolism, activation of the nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway as well as the AMPK pathway, and suppression of both the arachidonic acid pathway and the nuclear factor kappa B (NF-κB) inflammation pathway. Consequently, our research provides preliminary evidence that MG-Na displays promising anti-inflammatory and antioxidant properties for intervening in alcoholic liver disease (ALD), suggesting a viable path for ALD mitigation.