The oxygenation membrane, a core material of extracorporeal membrane oxygenation (ECMO), is facing challenges in balancing anti-plasma leakage, gas exchange efficiency, and hemocompatibility. Here, inspired by the asymmetric structural features of alveolus pulmonalis, a novel triple-functional membrane for blood oxygenation with a Janus architecture is proposed, which is composed of a hydrophobic polydimethylsiloxane (PDMS) layer to prevent plasma leakage, an ultrathin polyamide layer to enhance gas exchange efficiency with a CO2 :O2 permeance ratio of ≈10.7, and a hydrophilic polyzwitterionic layer to improve the hemocompatibility. During the simulated ECMO process, the Janus oxygenation membrane exhibits excellent performance in terms of thrombus formation and plasma leakage prevention, as well as adequate O2 transfer rate (17.8 mL min-1 m-2 ) and CO2 transfer rate (70.1 mL min-1 m-2 ), in comparison to the reported oxygenation membranes. This work presents novel concepts for the advancement of oxygenation membranes and demonstrates the application potential of the asymmetric triple-functional Janus oxygenation membrane in ECMO.