This study presents a novel sonosensitizer, copper-doped carbon dots (Cu-CDs), for sonodynamic therapy (SDT) in the treatment of glioblastoma multiforme (GBM). Cu-CDs, synthesized via a hydrothermal method, exhibit a p-n type semiconductor structure with a bandgap of 1.58 eV and a long carrier lifetime of 10.7 μs, enhancing their ability to generate reactive oxygen species (ROS) under ultrasound (US) irradiation. The Cu-CDs induce a unique form of cell death called cuproptosis, which involves copper toxicity and leads to proteotoxic stress and cell death. This mechanism synergizes with SDT to enhance therapeutic efficacy. Cu-CDs demonstrate excellent permeability through the blood-brain barrier (BBB) and potent anti-tumor activity, effectively inhibiting GBM tumor growth and prolonging mouse survival. In vitro and in vivo experiments confirm the effectiveness of Cu-CDs in inducing ROS and cell death, with significant tumor growth inhibition and improved survival rates in mice. The study highlights the potential of Cu-CDs as a promising sonosensitizer for SDT, offering a novel approach to treat GBM with enhanced therapeutic outcomes. The results suggest that Cu-CDs could be a valuable tool in the development of future therapies for glioblastoma.This study presents a novel sonosensitizer, copper-doped carbon dots (Cu-CDs), for sonodynamic therapy (SDT) in the treatment of glioblastoma multiforme (GBM). Cu-CDs, synthesized via a hydrothermal method, exhibit a p-n type semiconductor structure with a bandgap of 1.58 eV and a long carrier lifetime of 10.7 μs, enhancing their ability to generate reactive oxygen species (ROS) under ultrasound (US) irradiation. The Cu-CDs induce a unique form of cell death called cuproptosis, which involves copper toxicity and leads to proteotoxic stress and cell death. This mechanism synergizes with SDT to enhance therapeutic efficacy. Cu-CDs demonstrate excellent permeability through the blood-brain barrier (BBB) and potent anti-tumor activity, effectively inhibiting GBM tumor growth and prolonging mouse survival. In vitro and in vivo experiments confirm the effectiveness of Cu-CDs in inducing ROS and cell death, with significant tumor growth inhibition and improved survival rates in mice. The study highlights the potential of Cu-CDs as a promising sonosensitizer for SDT, offering a novel approach to treat GBM with enhanced therapeutic outcomes. The results suggest that Cu-CDs could be a valuable tool in the development of future therapies for glioblastoma.