Osteocalcin, a small non-collagenous protein predominantly synthesized by osteoblasts, plays a critical role in bone mineralization and metabolic regulation. As a vitamin K-dependent protein, it undergoes gamma-carboxylation post-translationally, enabling calcium binding to hydroxyapatite crystals during bone formation. Recent studies also highlight its endocrine functions, particularly in glucose metabolism and cognitive processes. Osteocalcin antibodies are essential tools for detecting and quantifying this protein in research and clinical settings. These antibodies are widely used in techniques like ELISA, Western blotting, and immunohistochemistry to study bone remodeling dynamics, osteoporosis, fracture healing, and metabolic disorders. Polyclonal antibodies offer broad epitope recognition, while monoclonal variants provide high specificity, making them suitable for differentiating between carboxylated (inactive) and uncarboxylated (hormonally active) osteocalcin isoforms. Species-specific antibodies (e.g., human, mouse, rat) enable cross-species comparative studies. Validation in relevant biological samples is crucial due to osteocalcin's low serum concentrations and structural variations. Emerging applications include investigating osteocalcin's role in diabetes, neurodegenerative diseases, and its crosstalk with organs like pancreas and brain. Reliable osteocalcin antibodies remain pivotal for advancing bone biology research and developing diagnostic/therapeutic strategies for skeletal and metabolic disorders.