Alcohol intake is associated with increased mortality worldwide, particularly liver diseases, making it imperative to explore innovative strategies for managing alcohol-related liver disease. In this study, the efficacy of Scytosiphon lomentaria fucoidan (SLF) in alleviating alcohol-induced liver injury was evaluated in a mouse model. It showed that SLF increased body weight and colon length, while reducing liver index, serum lipid, alanine aminotransferase, and aspartate aminotransferase in alcohol-treated mice. SLF inhibited inflammatory response in the liver by reducing inflammatory infiltration and the levels of pro-inflammatory cytokines. It can be associated with the alleviation of oxidative stress and the inhibition of the nuclear factor-κB pathway. SLF modulated alcohol-induced dysbiosis of gut microbiota, including a reduction in Bacteroidetes and Proteobacteria, and improved metabolites profile, primarily affecting short chain fatty acids and amino acids metabolism. In addition, SLF reduced the level of total bile acids, regulated the profile of bile acids, and increased the levels of farnesoid X receptor (FXR) and AMP-activated protein kinase (AMPK), suggesting that SLF can alleviate alcohol-induced liver injury by regulating bile acid-FXR/AMPK pathway. This study suggests that SLF holds the potential to alleviate the adverse effect of alcohol on the liver via the gut-liver axis.