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Acute pancreatitis (AP) is a common and serious acute inflammatory disease with high severity rate and mortality. Inflammation and oxidative stress play an extremely important role in the development of AP disease. Polyvinylpyrrolidone‐modified iridium nanoparticles (IrNP‐PVP) have multienzyme mimetic activity, and the aim of this article is to discuss the therapeutic alleviative effects of the ultrasmall nanozymes IrNP‐PVP on AP through their antioxidant and anti‐inflammatory effects. IrNP‐PVP were proved to inhibit inflammation and scavenge reactive oxygen species (ROS) at the cellular level. The synthetic IrNP‐PVP exhibit remarkable antioxidant and anti‐inflammatory activities in the prevention and treatment of AP mice by establishing murine AP model, which can reduce the oxidative stress and inflammatory response. The results of this article indicated that the ultrasmall nanozymes IrNP‐PVP effectively alleviate AP via scavenging ROS as well as suppressing inflammation both in vivo and in vitro, which might provide enormous promise for the AP management. [ABSTRACT FROM AUTHOR]