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The association between dipeptidyl peptidase-4 (DPP-4) inhibitors, known as gliptins, and acute pancreatitis raises growing concern. A systematic search of PubMed, Scopus and Web of Science was conducted for studies published between January 2005 and July 2024. Studies focusing on gliptin-induced pancreatitis were selected based on predefined criteria. While gliptins are effective in managing type 2 diabetes mellitus, several case reports and observational studies suggest a potential risk for inducing acute pancreatitis. Proposed mechanisms include increased pancreatic activity and cellular stress. Clinical presentation often includes abdominal pain and elevated pancreatic enzymes, necessitating prompt diagnosis and discontinuation of the offending agent. Early recognition and management, including discontinuation of the drug and supportive care, are crucial. Balancing benefits and risks of gliptin therapy is essential for ensuring patient safety and optimal outcomes. This review underscores the importance of vigilance among healthcare providers and the need for further research to develop safer therapeutic strategies.