Objective: This study was carried out to explore the protective effect of Sedum sarmentosum (SS) on alcoholic fatty liver disease (AFLD). Methods: We conducted an acute experiment in which female Kunming mice were given intragastric administration of alcohol to induce AFLD every 12 h, three times in total. Fresh SS were ground into homogenate for oral treatment, and the mice received ethanol and SS at the same time. The mice were sacrificed 4 h after the last alcohol administration, and serum and liver were collected for testing. We found that SS was effective and then carried out subsequent experiments. The dried SS was ground into powder and successively extracted by petroleum ether, ethyl acetate, methanol and water. The extracts of various polar solvents were used for treatment via intragastric administration. Results: The serum triglyceride levels in serum and liver were decreased with the administration of fresh SS. The methanol extract and water fractions had better therapeutic effect. Conclusion: Fresh SS can serve as an effective therapeutic of AFLD, and the high polar fractions were active.