There are various etiologies for hypoglycemia in patients with chronic renal failure, and its pathogenesis is complex. Concomitant use of medications is the most common cause. We report a rare case of an 82-year-old woman with type 2 diabetes mellitus in end-stage renal disease undergoing maintenance hemodialysis, who experienced recurrent symptomatic hypoglycemia during treatment with propoxyphene for pain relief. Hypoglycemia occurred simultaneously with elevated levels of serum immunoreactive insulin and C-peptide. After discontinuing propoxyphene, hypoglycemia mitigated and the level of insulin returned to normal range. Our case reminds us that propoxyphene-induced hypoglycemia should not be ignored, especially in hemodialysis patients with cold sweats, agitation and depressed consciousness.