<p>Protein is an essential nutrient in the human diet. Global Westernization and modern dietary trends have seen protein become a more substantial contributor to the Western diet, with dietary sources expanding beyond traditional wholefoods to a myriad of processed protein-enriched food products. Although dietary protein is critical for human health, it has also been implicated in colonic health and disease both directly via the microbial fermentation of protein entering the colonic environment and indirectly by affecting the intake of other nutrients in the diet such as fibre. Although protein digestion in the small intestine is highly efficient, there are numerous factors that can influence the capacity for protein digestion and absorption, particularly dietary factors representative of modern-day protein intakes such as high protein diets and food manufacturing. The subsequent fermentation of protein and production of microbial metabolites in the colon is in turn affected by the source of protein entering the colon and the presence of fibre. In this Review, we examine factors that influence human digestion and absorption of protein in the small intestine and protein fermentation in the colon, describing implications for colonic health and disease.</p>