Diabetes has become one of the major noninfectious diseases that seriously endanger public health. The formation of islet amyloid polypeptide (IAPP) affects the normal physiological functions of the body, such as glucose metabolism and lipid metabolism. The mature human IAPP protein (hIAPP) has a strong tendency to misfold and is considered to be one of the major causes of amyloid changes in islets. Deposition of hIAPP is considered to be one of the leading causes of type 2 diabetes mellitus (T2DM). Miniature pigs are experimental animal models that are well suited for research on gene function and human diabetes. In our study, we obtained IAPP gene-humanized miniature pigs via the CRISPR/Cas9 system and somatic cell nuclear transfer (SCNT) technology. The hIAPP pigs can be used to further study the pathogenesis and related complications of T2DM and to lay a solid foundation for the prevention and treatment of T2DM.