Abstract The inherent and unique charge‐carrier release characteristics of piezoelectric sonosensitizers with desired bandgap can be leveraged to initiate reactive oxygen species (ROS) reactions that have considerable potential for sonodynamic therapy (SDT). In this study, a bimetallic Bi 4 NbO 8 Br‐polyvinylpyrrolidone (BNOBP) with a small bandgap (2.45 eV) is synthesized as a potential piezoelectric sonosensitizer. The robust interactions within and between the Bi─O and Nb─O layers narrow the bandgap, facilitating carrier transfer. Concurrently, compared with that of TiO 2 and BiOBr, BNOBP exhibits a rapid acoustoelectric response and desirable electron–hole separation efficiency, enabling the generation of ·O 2 − under ultrasound (US) irradiation. Notably, BNOBP alleviates the overexpression of glutathione (GSH) in tumors and prevents the consumption of the generated ROS by GSH. Combining the previous small bandgap endow the high ROS generation efficiency, this study provides a paradigm for in situ regulation of oxidative stress levels in tumor tissue microenvironment based on bimetallic piezoelectric sonosensitizers.