The minipig has become a popular animal model in biomedical research. Minipigs offer advantages over domestic pigs due to their size and ease of handling, and offer a viable alternative to canine and non-human primates as a large animal model in the assessment of safety and toxicology of pharmaceutical compounds. Minipigs have similar anatomical and physiological features relative to humans, especially in regards to the gastrointestinal system. Despite the similarities to humans, minipigs also have key differences that should be considered in a research setting, discussed in this chapter. Furthermore, there are many available breeds of minipigs, and variations in breeds should be considered when working with minipigs in biomedical research. This chapter discusses the anatomy and physiology of the pig’s digestive system, as well as its use in surgical and efficacy research, pharmacology, and toxicology. It also discusses differences in absorption, and incidental toxicology findings in commonly used breeds of minipigs: Sinclair, Hanford, Yucatan, and Göttingen.