The aim of this study was to investigate the potential capability of an alcalase-hydrolyzed corn protein and fractions with different molecular mass (Mm) to facilitate alcohol metabolism by activating hepatic alcohol dehydrogenase (ADH). Results showed that corn peptide (CP) fraction with Mm fewer than 1,000 Da (CP < 1,000) exhibited the highest activity to activate ADH in vitro. The fraction administration (200 mg/kg body weight) with Mm fewer than 5,000 Da (CP < 5,000) demonstrated maximum ability to decrease blood alcohol concentration (BAC) in mice. There was a 45.1% reduction in BAC compared with that of the control group. Moreover, there was a strong linear relationship between BAC elimination rate and hepatic ADH activation rate (r = 0.9961). CP's potent capability to facilitate alcohol metabolism could be mainly correlated with the activation of hepatic ADH by hydrophobic CP with low Mm. CP's ·OH scavenging activity may also have synergistic contribution to the oxidative stress release.