AIM: To investigate the clinical characteristics of tramadol-induced hypoglycemia. METHODS: Case reports of tramadol-induced hypoglycemia were collected by searching Chinese and English data from the database establishment to April 28, 2023. RESULTS: Twenty patients were included, with a median age of 50 years (4, 88). Hypoglycemia occurred 1 h-23 d after tramadol administration, with a median blood glucose of 2.25 mmol/L  (0.22, 3.3) and a median daily dose of 300 mg (1.53, 14 000). The main clinical manifestations were unconscious (12 cases), multiple organ failure (7 cases), asystole and/or apnea (7 cases), seizures (4 cases), somnolence (3 cases) and sweating (3 cases).Tramadol concentrations were reported in 6 patients, with a median of 3.56 mg/L (0.47, 9.4). After stopping tramadol in 20 patients and giving symptomatic supportive treatment, 16 patients recovered, 1 patient had moderate brain dysfunction, and 3 patients died. CONCLUSION: Tramadol induced hypoglycemia can occur from 1 h to 23 d after administration, and can be clinically manifested as autonomic nervous system symptoms and neurohypoglycemia symptoms, mainly neurohypoglycemia symptoms. After stopping tramadol, most patients with hypoglycemia returned to normal, and severe patients can die.