In the past decade, mounting evidence points to the possibility of targeting bone for treating, preventing, and predicting type 2 diabetes mellitus. Osteoblast-derived osteocalcin (OCN) can stimulate insulin secretion, enhance insulin sensitivity, and favor glucose and fatty acid uptake and utilization. Lipocalin 2 is another osteokine secreted by osteoblasts and acts in appetite suppression. Neuropeptide Y may function in browning of white adipose tissue and energy expenditure. Osteocytes are proposed to have impact on the browning of white adipose tissue and energy expenditure through the secretion of bone morphogenetic protein 7 and sclerostin. Active bone resorption is also implicated in glucose homeostasis. In addition, there is evidence indicating the involvement of bone-derived receptor activator of nuclear factor κ-B ligand in the regulation of energy metabolism. We collect and summarize recent advances and the rationales for treating, preventing, and predicting diabetes by targeting skeleton. (Chin J Endocrinol Metab, 2018, 34: 543-548)