Rapid disinfection and promotion of bone regeneration are two crucial aspects of the clinical treatment of osteomyelitis. There is an urgent need to develop highly efficient bioactive sonosensitizers for sonodynamic therapy (SDT). Herein, a type of two-dimensional (2D) Nb₂C nanosheet-decorated porphyrin metal–organic framework hollow nanotubes (HNTM/Nb₂C) was designed to simultaneously eliminate infection and accelerate bone regeneration under ultrasound (US) irradiation. Building a Schottky junction between HNTM and Nb₂C nanosheets allowed enough reactive oxygen species (ROS) to be produced because of the rapid charge transfer and suppressed recombination of electron-hole pairs under US irradiation. The sonosensitizer accelerated the osteoblastic differentiation of stem cells. RNA-seq indicated that the HNTM/Nb₂C nanoplatform induced stem cell differentiation via cation transport and ATP-synthesis-coupled electron transport through an ultrasonic current. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the Nb ion may further improve osteogenesis via the activation of Wnt signaling. Our study provides novel strategies for improving SDT efficiency by simultaneously eliminating infections and promoting bone regeneration through US-current-combined ion therapy for osteomyelitis treatment.