Abstract: Objective To investigate the effect of type 2 diabetes (T2DM) on the clinical efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Methods A total of 441 patients with advanced NSCLC who received at least one dose of ICIs between 2019 and 2023 at the Affiliated Hospital of Xuzhou Medical University were included in the study. Based on whether they had T2DM, the patients were divided into two groups: a T2DM group (n=183) and a non-T2DM group (n=258). The T2DM group was further divided into two subgroups based on their fasting blood glucose (FBG) levels: group A (FBG≥7 mmol/L, n=108) and group B (FBG<7 mmol/L, n=75). Their characteristics and immune-related adverse events (irAEs) were retrospectively analyzed. The effect of T2DM on overall survival (OS) and progression-free survival (PFS) after ICIs treatment was performed by the Kaplan-Meier method. Results The T2DM group showed a higher proportion of patients aged over 60 years and a higher percentage of body mass index (BMI) ≥25 kg/m² than the non-T2DM group (P<0.05), with no statistical difference in pathological subtypes (P>0.05). There was no statistical difference in the incidence of irAEs between the two groups (P>0.05). The median PFS (7 months) and median OS (16 months) in the T2DM group were slightly shorter than those in the non-T2DM group (median PFS 9 months, median OS 17 months), with no statistical differences (P>0.05). In contrast, group B showed a significantly longer median PFS (11 months) and median OS (20 months) compared with group A (median PFS 6 months, median OS 12 months) (P<0.05). Conclusions There was no statistical difference between advanced NSCLC patients with T2DM and those without T2DM in terms of ICI treatment safety. Overall, T2DM do not significantly affect the efficacy of ICIs in advanced NSCLC patients. However, poorly controlled FBG significantly reduces the efficacy of ICIs treatment in T2DM patients.