This study explores the use of copper-doped carbon dots (Cu-CDs) as a novel sonosensitizer for sonodynamic therapy (SDT) in the treatment of glioblastoma multiforme (GBM). Cu-CDs, synthesized through a one-step hydrothermal process, exhibit enhanced sonodynamic properties due to their p-n type semiconductor structure, a reduced bandgap of 1.58 eV, and an extended carrier lifetime of 10.7 μs. These properties improve the separation of electrons and holes, leading to increased reactive oxygen species (ROS) generation upon low-intensity ultrasound (US) irradiation. Cu-CDs induce cuproptosis, a copper-dependent non-apoptotic cell death mechanism, which synergizes with SDT to enhance therapeutic efficacy. In vitro and in vivo studies demonstrate that Cu-CDs effectively cross the blood-brain barrier (BBB), accumulate in the brain, and significantly inhibit GBM growth while prolonging the survival of tumor-bearing mice. The combination of Cu-CDs and SDT shows promising potential for the treatment of GBM, offering a novel and effective approach to address the challenges in cancer therapy.This study explores the use of copper-doped carbon dots (Cu-CDs) as a novel sonosensitizer for sonodynamic therapy (SDT) in the treatment of glioblastoma multiforme (GBM). Cu-CDs, synthesized through a one-step hydrothermal process, exhibit enhanced sonodynamic properties due to their p-n type semiconductor structure, a reduced bandgap of 1.58 eV, and an extended carrier lifetime of 10.7 μs. These properties improve the separation of electrons and holes, leading to increased reactive oxygen species (ROS) generation upon low-intensity ultrasound (US) irradiation. Cu-CDs induce cuproptosis, a copper-dependent non-apoptotic cell death mechanism, which synergizes with SDT to enhance therapeutic efficacy. In vitro and in vivo studies demonstrate that Cu-CDs effectively cross the blood-brain barrier (BBB), accumulate in the brain, and significantly inhibit GBM growth while prolonging the survival of tumor-bearing mice. The combination of Cu-CDs and SDT shows promising potential for the treatment of GBM, offering a novel and effective approach to address the challenges in cancer therapy.