Fluoroquinolones are commonly prescribed antimicrobials that have been implicated in alterations of glucose metabolism. We report a case of refractory fluoroquinolone-induced hypoglycemia in a patient with type-2 diabetes mellitus on glipizide that was successfully treated with octreotide. A patient was admitted with hypoglycemia after having been initiated on levofloxacin therapy. Despite treating the hypoglycemia supportively with multiple boluses of 25 g of dextrose, a continuous dextrose infusion, and glucagon, the patient experienced repeated episodes of rebound hypoglycemia. The persistent hypoglycemia was eventually reversed with the administration of subcutaneous octreotide. Clinicians should be cognizant of this adverse effect of fluoroquinolones, as well as predisposing risk factors, and consider octreotide as an adjunctive therapy for refractory hypoglycemia cases.