Maintaining bone homeostasis relies on the balance between bone remodeling involving bone resorption by osteoclasts and bone formation by osteoblasts under physiological conditions. An increasing number of studies have shown that the ubiquitin-proteasome system plays an important role in bone remodeling. The ubiquitination process is reversible through the action of deubiquitinase (DUB), and ubiquitin-specific proteases (USPs) are the largest of the DUB families. This article summarizes the mechanisms by which USPs regulate bone homeostasis, including USP4 and USP7, by affecting bone formation through signaling pathways such as Wnt/β-catenin and cylindromatosis (CYLD) and regulating bone resorption through signaling pathways such as nuclear factor-kappa B (NF-κB). In addition to affecting bone resorption and bone formation during bone reconstruction, the effect of USPs on bone is also reflected in the osteogenic differentiation of human periodontal membrane stem cells and implant bone binding. Future research should determine whether USPs have a greater regulatory effect on bone reconstruction and the specific mechanism of their regulatory effect to provide more approaches for the treatment of bone diseases.