I report a severe prolonged hypoglycemia side effect of the often-used drug hydroxychloroquine in a nondiabetic elderly woman with undifferentiated connective tissue disease. Although the mechanism of lowering blood glucose levels has not been clarified yet, but severe and prolong hypoglycemia need to be keep in mind. Therefore, in clinical practice, we must be careful when prescribe this drug for patients and check glucose levels in the initial phase. Education on hypoglycemia self-management may also be performed.