AbstractChinese herbal medicine has well‐established therapeutic effects in various diseases. Corilagin (Cor), a gallic acid tannin in Phyllanthus niruri L., has anti‐inflammatory and antioxidant effects in many diseases. However, its role in osteoclast‐related bone diseases has not been determined. In vitro, bone marrow macrophages (BMMs) were extracted and isolated to differentiate into osteoclasts. The effects of Cor on osteoclast formation, bone resorption, and reactive oxygen species (ROS) production were performed. In addition, quantitative real‐time polymerase chain reaction and western blot analysis were used to evaluate the effect of Cor on oxidative stress‐related pathways, which are nuclear factors‐κB ligand‐receptor activator (RANKL) stimulates important downstream pathways. Furthermore, microcomputed tomography and bone histomorphometry were performed to analyze the therapeutic effect of Cor in mouse models of lipopolysaccharide (LPS)‐mediated bone defects in vivo. Cor influenced the nuclear factor of activated T cells 1 (NFATc1) signaling pathway and reduced ROS in RANKL‐treated osteoclasts, thereby inhibiting osteoclast formation and bone resorption. Moreover, Cor protected against LPS‐mediated skull defects in vivo. In sum, our results confirm that Cor can inhibit osteoclastogenesis and intracellular oxidative stress. In addition, the inflammatory bone defect induced by LPS was also attenuated by Cor. Accordingly, Cor is a new candidate therapeutic agent for osteoclast‐mediated osteolytic diseases.