Predominant health impacts from alcoholism are chronic neurologic deficits and hepatic dysfunction. Pueraria extract (PE) is a solution obtained from the dried root of Pueraria lobate and can reverse alcohol-induced hepatic damage. The present study aimed to elucidate the effects of PE on ethanol-induced injury in microglia and neurons. To confirm the reliability of the experimental approach, an in vivo demonstration of PE activity was used to verify its impact on hepatic damage in mice exposed to ethanol (ETOH). Subsequently, an in vitro assay was used to verify the effects of PE on ETOH-exposed microglia and neurons.PE reversed fibrosis and hyperplasia, adipocyte infiltration, hepatomegaly, hepatic function, lipid metabolism, indicators of oxidative stress, and morphological changes in hepatic cells, induced by ETOH exposure. The reliability of the experimental approach was thus confirmed. PE also reversed the activation of microglia and inflammatory-related cytokines and proteins induced by ETOH exposure. PE showed protective effects on neurons via inhibition of mitochondrial fission. in vivo and in vitro evidence indicated that PE might be useful in the treatment of both hepatic injury and neurologic deficits commonly observed in chronic alcoholism.