The small intestine is a highly differentiated and complex organ with many nutritional, physiological, and immunological functions [1–8]. First, the small intestine is responsible for the terminal digestion and absorption of dietary nutrients and is, therefore, essential to health, growth, development, reproduction, and sustaining life in organisms. Second, the neonatal small intestine can absorb immunoglobulins from milk before gut closure, which is important for the immunity of newborns. Third, the gut separates the internal milieu of organisms from their external environment, which is critical for the exclusion of food-borne pathogens and preventing the translocation of luminal microorganisms into the blood circulation. Finally, as the largest lymphoid organ in mammals, the small intestine participates in the immune surveillance of the intestinal epithelial layer and the regulation of mucosal responses to foreign antigens. In contrast to the small intestine, the large intestine harbors large amounts of microorganisms that ferment carbohydrates, proteins, and amino acids (AAs) to form short-chain fatty acids, H2S, ammonia, indoles, skatole, and other metabolites. In addition, unlike the small intestine, the large intestine is susceptible to the development of tumors. Thus, nutrients are major factors affecting gut health and function, as well as whole-body metabolism and homeostasis in humans and animals. Some of these advances are highlighted in this Special Issue of the International Journal of Molecular Sciences entitled “Nutrition and Gut Health”[1–8]. Its specific topics include the roles of dietary carbohydrates [1, 2], AAs [3, 4], lipids [5, 6], and non-nutrient bioactive molecules [7, 8] in animal models such as pigs, rats, and mice.