Low-intensity pulsed ultrasound (LIPUS) is a common physical therapy to accelerate the healing of bone fracture and treat delayed union of bone fracture. Vessels, nerves, and bone tissue are essential constituents of bone system. Recently, increasing evidence has been revealed that LIPUS can not only promote bone regeneration by directly regulating osteoblasts, osteoblasts, mesenchymal stem cells, but also have a positive impact on the repair of bone healing through vessels and nerves. Thus, we reviewed and summarized the latest published literature about the molecular mechanism for the effects of LIPUS on bone regeneration, which might offer a promising therapy for bone-related diseases.