Osteocalcin (OC) is a non-collagenous protein produced by osteoblasts, consisting of carboxylated (cOC) and undercarboxylated (ucOC) forms. cOC promotes bone mineralization and strength, while ucOC is an endocrinologically active form with multiple functions in various tissues. Total OC (tOC) includes both forms and is used as a marker of bone turnover. This review aims to summarize current knowledge about OC and its role in diabetes mellitus, osteoporosis, osteopetrosis, and inflammatory joint diseases, focusing on clinical studies and the involvement of pharmacological treatments. Lower levels of tOC and ucOC are associated with an increased risk of type 2 diabetes mellitus, but tOC does not accurately reflect bone turnover in postmenopausal osteoporosis, osteoarthritis, and rheumatoid arthritis. Pharmacological treatments for these conditions can affect OC levels, potentially influencing glucose metabolism, body weight, adiponectin secretion, and synovial inflammation. The review highlights the need for further research to elucidate the role of OC in human health and disease, particularly in larger patient cohorts and through genetic studies.Osteocalcin (OC) is a non-collagenous protein produced by osteoblasts, consisting of carboxylated (cOC) and undercarboxylated (ucOC) forms. cOC promotes bone mineralization and strength, while ucOC is an endocrinologically active form with multiple functions in various tissues. Total OC (tOC) includes both forms and is used as a marker of bone turnover. This review aims to summarize current knowledge about OC and its role in diabetes mellitus, osteoporosis, osteopetrosis, and inflammatory joint diseases, focusing on clinical studies and the involvement of pharmacological treatments. Lower levels of tOC and ucOC are associated with an increased risk of type 2 diabetes mellitus, but tOC does not accurately reflect bone turnover in postmenopausal osteoporosis, osteoarthritis, and rheumatoid arthritis. Pharmacological treatments for these conditions can affect OC levels, potentially influencing glucose metabolism, body weight, adiponectin secretion, and synovial inflammation. The review highlights the need for further research to elucidate the role of OC in human health and disease, particularly in larger patient cohorts and through genetic studies.