With the increasing incidence of inflammatory bowel disease (IBD), antioxidant therapies aimed at scavenging excess reactive oxygen species (ROS) are considered promising treatment options. However, current strategies, such as the use of natural antioxidants or synthetic nanozymes, are often limited by inefficient biological delivery and potential safety concerns. To address these challenges, we developed OFn-EcN (OmpA-Ferritin nanozymes expressed in EcN), a novel biosynthetic system that integrates natural ferritin nanozymes with the beneficial probiotic (EcN). Specifically, biosynthesized ferritin nanozymes exhibit superoxide dismutase- and catalase-like activities to scavenge ROS in a cascade. Upon oral administration, OFn-EcN effectively neutralizes excessive ROS in the gut, protecting against probiotics and breaking the vicious cycle of inflammation and oxidative damage. Furthermore, the system restores intestinal barrier integrity, enhances nutrient absorption, and reestablishes a healthy microbial balance with a low risk of extraintestinal dissemination and high biosafety. In preclinical models, OFn-EcN effectively prevented the onset of DSS-induced colitis. Thus, this innovative approach offers a promising strategy for the prevention and effective alleviation of IBD.