Osteocalcin (OCN), a non-collagenous protein synthesized by osteoblasts, is integral to bone mineralization and demonstrates significant effects on metabolic and neurological functions. Its undercarboxylated form, Glu-OCN, has emerged as a key regulator of glucose metabolism in diabetes, bone density in osteoporosis (OP), and lipid metabolism in conditions such as nonalcoholic fatty liver disease (NAFLD). Additionally, Glu-OCN is implicated in neurodegenerative and cardiovascular diseases through its roles in neurotransmitter synthesis and vascular calcification, respectively. This review examines the essential functions of Glu-OCN in the management of metabolic and neurodegenerative disorders, emphasizing its significance as both a diagnostic biomarker and therapeutic target. While findings to date are promising, most studies remain observational. Advanced detection methodologies and extensive longitudinal studies are urgently needed to elucidate the mechanisms and clinical applications of Glu-OCN. Advancements in this area could facilitate the integration of Glu-OCN into personalized medicine approaches, improving early diagnosis, risk assessment, and treatment monitoring.