Medical catheters are susceptible to biological contamination and pathogen invasion, leading to infection and inflammatory complications. The development of antimicrobial coatings for medical devices has emerged as a promising strategy. However, limited biological functionality and the incompatibility between bactericidal properties and biosafety remain great challenges. Herein, a multifunctional polymer coating (CPB‐Ac) is created, incorporating an ultrasonic‐responsive carbon monoxide release unit (CORM‐Ac) and antifouling unit to treat catheter‐related complications. As‐synthesized CPB‐Ac polymer can be stably anchored to various medical devices with arbitrary shapes and compositions via facile UV treatment. Both in vivo and vitro experiments demonstrated that this multi‐functional coating exhibits anti‐fouling, anti‐inflammatory, and broad‐spectrum antibacterial activities as well as good biosafety. During the initial implantation phase, the antifouling units of CPB‐Ac coating effectively inhibit the attachment of biological contaminants, significantly reducing the risk of thrombosis and bacterial infection. Once bacterial infection occurs, ultrasonic irradiation can activate CPB‐Ac coating to release CO with a much higher amount of 55.3 µm than non‐ultrasound controls, therefore rapidly eliminating bacteria and alleviating inflammatory response. It is believed that the work may provide an effective method for the development of next‐generation intelligent medical coatings against catheter‐related complications.