BACKGROUND/OBJECTIVES: Ileitis, or inflammation of the terminal ileum, is often linked to inflammatory bowel disease (IBD), especially Crohn's disease, but may also arise from non-steroidal anti-inflammatory drug (NSAID) use. While NSAIDs are known to cause gastrointestinal injury, their role in ileitis and downstream metabolic consequences remains unclear. This study evaluated the relationship between NSAID use, biopsy-confirmed ileitis, and glucose metabolism abnormalities in patients with and without IBD. METHODS: We conducted a retrospective cohort study of 3725 adults who underwent ileal biopsy between 2009 and 2022 at a tertiary care center. Patients were stratified based on histologic evidence of ileitis. Collected data included demographics, IBD status, NSAID and steroid use, hemoglobin A1C, fasting glucose, and diagnoses of abnormal glucose metabolism. Multivariable logistic and linear regression models adjusted for age, BMI, sex, steroid use, and IBD. RESULTS: Of 3725 patients, 876 had biopsy-confirmed ileitis. NSAID use-categorized as current, historical, or inpatient-was not significantly associated with ileitis after adjustment. In contrast, IBD was the strongest independent predictor (p < 0.05). Although unadjusted analyses showed lower A1C in the ileitis group (p = 0.003), this was not significant after controlling for confounders (p = 0.084). No significant associations were found between ileitis and fasting glucose or abnormal glucose metabolism. Age and BMI were the dominant predictors of glycemic abnormalities. CONCLUSIONS: NSAID use was not associated with biopsy-confirmed ileitis or impaired glucose metabolism. Traditional metabolic risk factors were stronger predictors of glycemic abnormalities than localized ileal inflammation.