<p>The treatment of infectious arthritis faces multiple challenges, including the exacerbation of traditional antibiotic resistance and the difficulty of regulating the tissue microenvironment. In this study, the FeS/CeO₂/Cur (curcumin) heterostructure was constructed through interface engineering, and an ultrasonic (US) responsive nanotherapeutic platform was proposed, which combined sonodynamic-H₂S antibacterial action with US modulated nanozyme activity. FeS/CeO₂/Cur integrated the intrinsic redox properties of Ce³⁺/Ce⁴⁺ with the piezoelectric catalytic effect. Under US irradiation, FeS/CeO₂/Cur nanozyme exhibited an interface-enhanced piezoelectric effect. It generated ·O₂⁻ and ·¹O₂ radicals through piezoelectric catalytic activity, while achieving the US-responsive release of H2S. The Ce³⁺/Ce⁴⁺ dynamic equilibrium system triggered shows US modulated antioxidant properties, which can scavenge pathogenic ROS by Ce³⁺/Ce⁴⁺ redox cycling during the interface. FeS/CeO₂/Cur's sonodynamic antibacterial activity revealed that it achieved broad-spectrum sterilization by disrupting bacterial ATP metabolism and regulating related genes, including <i>narG</i>, <i>purM</i>, and <i>narJ</i>. The in vivo bacterial arthritis model also confirmed that FeS/CeO₂/Cur can eliminate bacteria rapidly and promote osteogenic differentiation, providing an effective treatment strategy for infectious arthritis.</p> Graphical abstract <p></p>