Dietary protein is a vital nutrient for humans and animals, which is primarily digested into peptides and free amino acids (FAAs) in the upper gastrointestine with the help of proteases. The products are absorbed by the enterocytes and are metabolized in different organs of body. Dietary protein, peptides and FAAs that escape digestion and absorption of the small intestine will enter the large intestine for further fermentation by the vast gut microbiota. Particularly, amino acid (AAs) metabolism by bacteria occurs via either deamination or decarboxylation reactions and generates short chain fatty acids (SCFAs) or amines, respectively. These metabolites elicit a wide range of biological functions via different receptors and mechanisms. This review discusses the interaction between protein metabolites and gastrointestine, illustrates regulation of intestinal motility and immune response by SCFAs and their receptors, and focuses on modulation of intestinal inflammation and signal transduction by biogenic amines (BAs) involving polyamines and monoamine neurotransmitters.