AbstractSonodynamic therapy (SDT) has demonstrated significant potential in addressing multidrug‐resistant bacterial infections due to its noninvasive nature and independence from antibiotics and light sources. However, the majority of current sonosensitizers exhibit aggregation‐caused quenching (ACQ), leading to low reactive oxygen species (ROS) generation efficiency. Herein, a novel nonplanar structured sonodynamic (4,4‐difluoro‐4‐boron‐3a,4‐diaza‐indandiene) BODIPY derivative, BODN, with aggregation‐induced emission (AIE) properties, and rapid generation of substantial ROS by ultrasound is introduced. The BODN is co‐assembled with the commercial amphiphilic polymer, mDSPE‐PEG2000, forming BODN nanoparticles (BODN‐NP). Under ultrasound conditions, BODN‐NP demonstrates potent antimicrobial activity and improves the inflammatory response to promote healing wounds infected by both Staphylococcus aureus and methicillin‐resistant Staphylococcus aureus. This work expands the use of AIE sonodynamic materials in antimicrobial therapy and provides new perspectives for innovative solutions against multidrug‐resistant bacterial infections.