Abstract Infectious bone defects represent a substantial challenge in clinical practice, necessitating the deployment of advanced therapeutic strategies. This study presents a treatment modality that merges a mild photothermal therapy hydrogel with a pulsed drug delivery mechanism. The system is predicated on a hydrogel matrix that is thermally responsive, characteristic of bone defect sites, facilitating controlled and site-specific drug release. The cornerstone of this system is the incorporation of mild photothermal nanoparticles, which are activated within the temperature range of 40–43 °C, thereby enhancing the precision and efficacy of drug delivery. Our findings demonstrate that the photothermal response significantly augments the localized delivery of therapeutic agents, mitigating systemic side effects and bolstering efficacy at the defect site. The synchronized pulsed release, cooperated with mild photothermal therapy, effectively addresses infection control, and promotes bone regeneration. This approach signifies a considerable advancement in the management of infectious bone defects, offering an effective and patient-centric alternative to traditional methods. Our research endeavors to extend its applicability to a wider spectrum of tissue regeneration scenarios, underscoring its transformative potential in the realm of regenerative medicine.