Birds exhibit naturally high blood glucose concentrations, a physiological trait that, unlike in mammals, does not lead to typical pathological consequences such as diabetes mellitus. This review explores the unique features of glucose metabolism in birds, with a particular focus on the anatomy and function of the avian pancreas, the roles of key hormones such as insulin and glucagon, as well as the distinctive mechanisms of glucose absorption and utilization. Evidence suggests a dominant role of glucagon over insulin, along with adaptations such as insulin resistance and antioxidant defenses, which may contribute to birds’ apparent resilience to hyperglycemia-related complications. Despite these adaptations, cases of diabetes mellitus have been reported, primarily as secondary to other pathologies, including pancreatitis, hemochromatosis, infections, and toxicities. Diagnosis remains challenging due to interspecies variability and the lack of standardized assays. Treatment, mainly via insulin therapy, has shown mixed outcomes, often limited by the underlying disease severity. This review highlights the need for species-specific diagnostic tools and a deeper investigation into the pathophysiology of glucose regulation in birds, aiming to improve clinical outcomes, develop standardized therapies, and ultimately broaden the perspectives of comparative endocrinology.