Background: Hypoglycemia is one of the most fatal complications during the perioperative period. General anesthesia or sedation can mask a hypoglycemia-altered mental status. Acute hypoglycemia might result in permanent brain injury. There is no way to detect hypoglycemia during general anesthesia, except for intermittent blood glucose monitoring. Case presentation: Hypoglycemia is associated with changes in electroencephalogram readings. Here, we report two cases of patients with an abnormally low Bispectral Index (BIS) associated with diabetic retinopathy surgery, one in the recovery stage of general anesthesia and the other in the maintenance of general anesthesia. Hemodynamics were stable. Severe hypoglycemia (1.6 mmol/L and 2.2 mmol/L) was then detected. BIS increased with the correction of severe hypoglycemia. Conclusions: For diabetic patients, when the intraoperative BIS value is abnormally low, hypoglycemia should be considered. Severe hypoglycemia may be presented in BIS monitoring during general anesthesia.