AbstractMesenchymal stem cells (MSCs) play a crucial role in maintaining bone homeostasis and are extensively explored for cell therapy in various bone‐related diseases. In addition to direct cell therapy, the secretion of extracellular vesicles (EVs) by MSCs has emerged as a promising alternative approach. MSC‐derived EVs (MSC‐EVs) offer equivalent therapeutic efficacy to MSCs while mitigating potential risks. These EVs possess unique properties that enable them to traverse biological barriers and deliver bioactive cargos to target cells. Furthermore, by employing modification and engineering strategies, the therapeutic effects and tissue targeting specificity of MSC‐EVs can be further enhanced to meet specific therapeutic needs. In this review, the mechanisms and advantages of MSC‐EV therapy in diseased bone tissues are highlighted. Through simple isolation and modification techniques, MSC‐EV‐based biomaterials have demonstrated great promise for bone regeneration. Finally, future perspectives on MSC‐EV therapy are presented, envisioning the development of next‐generation regenerative materials and bioactive agents for clinical translation in the field of bone regeneration.