Catheter-associated urinary tract infection (CAUTI) presents a significant clinical challenge globally, given its elevated infection risk, substantial treatment costs, and the emergence of drug-resistant strains. Despite extensive clinical endeavors, such as the development of antimicrobial catheters and prophylactic approaches, addressing CAUTI remains intricate due to the microenvironment complexity, sustained antimicrobial requirements, the necessity for antibiofilm strategies, and concurrent inflammatory responses. Herein, an innovative solution involving an ultra-low loading gold/iron co-doped silver peroxide nanozyme-reinforced hydrogel coating is introduced for the prevention of CAUTI. The silicone urinary catheter is modified through a straightforward and cost-effective chemical process to impart multienzyme-like activities, including peroxidase- and catalase-like functions, which exhibit antimicrobial, antibiofilm, and anti-inflammatory properties tailored to the unique urinary tract microenvironment. Additionally, the hydrogel coating enhances the hydrophilicity of catheter, thereby improving patient comfort. In vitro and in vivo experiments substantiate the efficacy of the modified catheter in inhibiting bacterial colonization, curtailing biofilm formation, enhancing oxygen supply, and modulating immune responses. This study not only proposes an alternative strategy for prevention and treatment of CAUTI but also provides a promising therapy that addresses multifaceted therapeutic needs through the utilization of multienzyme-like nanozymes.