Alcoholic fatty liver disease (AFLD) is caused by long-term heavy alcohol consumption; therefore, useful and practical methods for the prevention of AFLD are urgently needed. The edible flower of Dendrobium officinale contains diverse flavonoids, and has shown antioxidant activity as well as antihypertensive and anti-inflammatory effects. In this study, an AFLD model was established, the protective effect of D. officinale flower (DOF) ethanol extract on AFLD was evaluated, and its mechanisms were investigated by analyzing gut microbiota and short-chain fatty acids (SCFAs). DOF extract (DOFE) supplementation promoted alcohol metabolism, restored hepatic antioxidant capacity, alleviated oxidative stress, reduced inflammatory factor levels, and inhibited dyslipidemia induced by alcohol intake in chronic alcohol-exposed mice, especially in the high DOFE group. Moreover, DOFE supplementation increased the diversity, structure, and composition of the gut microbiota in mice, restored some of the abnormal SCFA levels caused by AFLD, and helped restore intestinal function. DOFE supplementation significantly increased the relative abundance of Akkermansia, suggesting that Akkermansia may be a potential target of the protective effect of DOFE. Therefore, DOFE supplementation to improve the composition of the gut microbiota may be an effective therapeutic strategy for the prevention of AFLD.