Brain-bone axis is an emerging concept in the interdisciplinary field of neuroscience and skeletal biology, revealing a complex and bidirectional regulatory network between the central nervous system and skeletal system. This article systematically reviews the core insights of the brain-bone axis, and delves into the mechanisms by which brain regulates skeletal homeostasis through neural, endocrine, and immune pathways and the feedback effects of skeleton (functioning as an endocrine organ) on brain function. This review also outlines the spectrum of diseases closely associated with dysfunction of the brain-bone axis, including neurodegenerative disorders, psychiatric conditions, and metabolic bone diseases. Furthermore, the article focuses on the potential clinical intervention strategies derived from brain-bone axis theory, aiming to provide new theoretical foundation and strategic perspective for integrated cross-system therapeutic approaches to related diseases.