Refractory hypoglycemia in non-diabetic patients is a rare condition characterized by low blood glucose levels (< 70 mg/dL) that do not respond to the conventional treatment. It can be caused by serious underlying issues such as liver failure, adrenal insufficiency, insulin-secreting tumors, or sepsis. This form of hypoglycemia requires rapid interventions to avoid severe neurological complications. Management involves addressing the underlying cause and providing supportive measures such as glucose infusion or pharmacological agents like glucocorticoids or diazoxide. A multidisciplinary approach and early identification are key to improving the prognosis of affected patients.