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Objective: To determine whether diabetes mellitus (DM) contributes to the drug resistance of carbamazepine (CBZ), we investigated the correlation between the blood glucose status and the CBZ resistance condition in patients with trigeminal neuralgia (TN). Patients and methods: A total of 155 TN patients treated with the CBZ monotherapy were selected at Shanghai General Hospital and Shanghai Xinhua Hospital from September 2018 to January 2020. Among them, 15 were diagnosed with DM. Patients' CBZ resistance levels were evaluated according to progression-free survival. We utilized ordered multiple classification logistic regression to determine the dominant factors leading to CBZ resistance. We analyzed the correlation between hemoglobin A1c (HbA1c) and progression-free survival using the Pearson correlation analysis. Results: The regression analysis showed that DM was the only factor affecting CBZ resistance (p = 0.035; OR = 0.327; 95% CI, 0.115–0.926). Progression-free survival was 28.5 ± 21.2 months in the DM group and 66.0 ± 33.2 months in the non-DM group. The concentration of HbA1c in the blood was negatively correlated with progression-free survival (r = − 0.197; p = 0.014). Conclusions: This study shows that blood glucose status is a significant factor contributing to the CBZ resistance in the treatment of TN. The progression-free survival of patients is affected by the status of DM and blood HbAlc levels. [ABSTRACT FROM AUTHOR]