OBJECTIVES: Acute alcohol intoxication is characterized as high morbidity and mortality. To explore new chemicals to relieve ethanol intoxication, we tried to explore the activators of catalase (CAT), an enzyme responsible for oxidization of ethanol into acetaldehyde to accelerate ethanol removal. METHODS: We identified zanamivir, an antiviral agent, activated CAT in vitro after screening of clinical chemicals. Then, female KunMing mice were administrated with a single dose of ethanol to induce acute alcoholism model. The behavioral changes were recorded, besides, the serum ethanol derivatives and redox- associated with indexes in mouse liver were detected. RESULTS: We observed that zanamivir augmented CAT activity to reduce blood ethanol concentration. Mechanically, zanamivir enhanced superoxide dismutase (SOD) activity and glutathione (GSH) amount, meanwhile it decreased the concentration of malondialdehyde (MDA), thereby mitigating oxidative damage induced by ethanol consumption. Accordingly, zanamivir relieved drunkenness in mouse ethanol intoxication model, and simultaneously suppressed aspartate transferase (AST), alanine transaminase (ALT) and lactic acid (LD) accumulation to protect hepatic function and tissue. SIGNIFICANCE: Collectively, our work suggests that zanamivir should be repurposed for countering alcohol intoxication in clinic.