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This multicenter retrospective study evaluated the impact of type 2 diabetes mellitus (DM) on clinical outcomes and immune-related adverse events (irAEs) in 450 patients with metastatic non-small cell lung cancer (NSCLC) treated with second-line nivolumab at 17 centers between 2016 and 2024. Among these patients, 118 (26.2%) had DM. Baseline demographic and clinical characteristics, including age, sex, smoking status, ECOG performance status, histology, and PD-L1 expression, were similar between patients with and without DM. Nivolumab demonstrated similar antitumor activity in both groups, with no significant differences in median progression-free survival (PFS), overall survival (OS), or objective response rates. However, the incidence of Grade 3-4 irAEs was significantly higher in patients with DM. HbA1c levels were not associated with survival outcomes in univariate analyses, and metformin or insulin use did not affect PFS or OS among patients with DM. These findings indicate that DM does not compromise immunotherapy efficacy but is associated with a higher risk of severe toxicity. Clinicians should consider metabolic status and closely monitor patients with DM receiving immunotherapy. Further prospective studies are needed to clarify underlying mechanisms and optimize treatment strategies for this population.