Osteocalcin (OC) is the most abundant non-collagenous protein within the bone matrix. Since 2007, with evidence mostly from genetically modified mouse models, it was suggested that undercarboxylated form of OC (ucOC) acts as a hormone involved in energy metabolism, male fertility, muscle mass regulation, and cognition. However, several studies with alternative OC knockout (KO) rodent models did not support earlier findings. Herein, we investigated whether ucOC is linked to glucose regulation and insulin sensitivity by examining the observational evidence in humans, as well as the evidence obtained from exogenous ucOC treatment models (in vivo, ex vivo and in vitro), independent of data generated via genetically modified animal models. Overall, in humans, there is a substantial amount of evidence linking lower circulating ucOC levels with increased adiposity and increased risk of type 2 diabetes. Furthermore, there is an increasing body of evidence showing that exogenous treatment with ucOC improves whole-body and skeletal muscle glucose metabolism. Conflicting results reported may be related to methodological differences between studies, such as type/source of animal and cell culture models, source/origin of exogenous ucOC, dose and duration of ucOC treatment. However, whether the reported effects of ucOC on glucose regulation is clinically significant is yet to be determined.