Osteocalcin is no longer regarded as a molecule exclusive to bone remodeling and osteogenesis, but as a hormone with manifold functions. The discovery of the interaction of osteocalcin with the G protein-coupled receptor family C group 6-member A (GPRC6A) receptor has accompanied the characterization of several roles that this peptide serves in body regulation and homeostasis. These roles include the modulation of memory in the brain, fertility in the testis, fat accumulation in the liver, incretins release in the intestine and adaptation to exercise in muscle, in addition to the well-known effects on β-cell proliferation, insulin release and adiponectin secretion. The aim of the present review was to provide a practical update of the multi-organ effects that osteocalcin exerts through its interaction with GPRC6A and the clinical implications of this.