INTRODUCTION: Recent-onset colitis poses a diagnostic challenge, necessitating a thorough evaluation to identify potential infectious and non-infectious etiologies. We considered inflammatory bowel disease (IBD) secondary to dipeptidyl peptidase 4 (DPP-4) inhibitor-induced colitis. CASE PRESENTATION: This case report details the presentation and management of a patient with persistent dysentery, refractory to conventional treatments, ultimately attributed to IBD possibly secondary to long-term DPP-4 inhibitor use. Following an episode of suspected amebiasis, the patient experienced prolonged bloody diarrhea with an endoscopic image compatible with ulcerative colitis. Extensive infectious diagnostics were negative. Ultimately, the cessation of sitagliptin therapy resulted in rapid symptom resolution and normalization of eosinophilia, as well as endoscopic improvement. However, after a few weeks, the patient was readmitted with diarrhea after continued cessation of sitagliptin. CONCLUSION: This case underscores the importance of considering IBD secondary to DPP-4 inhibitor use in the evaluation of patients with recent-onset IBD. Further research is needed to elucidate the pathophysiological mechanisms underlying the relationship between DPP-4 inhibitors and IBD.