The implantation of ureteral stents frequently induces complications, such as bacterial biofilm formation and stone deposition, which are caused by bacterial adhesion on the stent surface and also urease-driven urinary alkalization. Conventional antimicrobial strategies, including drug-eluting or hydrophilic coatings, offer passive protection and may result in antibiotic resistance. To overcome these limitations, we developed a new hydrophilic lubricating coating with the synergistic function of antibacterial adhesion and urease-responsive bactericidal ability. The coating, based on urease-catalyzed urea hydrolysis, embedded sulfamethoxazole, which remained inactive until urease hydrolyzed the urea bond. By investigation of the microscopic adhesion forces, the coating was proven to have excellent antibacterial adhesion ability. Furthermore, from both in vitro and in vivo tests with typical urease-active bacteria, the coating showed remarkable urease-responsive bactericidal performance. This design enhanced antimicrobial efficacy while reducing toxicity and nonspecific release, thereby offering significant potential for improving the performance of ureteral stents.