The human intestine is a very complicated environment, with many residing microbial communities which form the gut microbiota. Normally, gut microbes and their hosts live peacefully with mutual benefits. The balance between the host and the gut microbiota largely relies on the homeostasis of the intestinal mucosa, which consists of a mechanical barrier made of epithelial cells, lamina propria, and a thin layer of smooth muscle called the muscularis mucosa. The intestinal mucosa, together with its self-secreted mucus layer, the mucosal immune system, and the commensal gut microbiota, form the intestinal mucosal barrier that can defend against external adversities such as pathogenic bacterial infections. Here, we retrospect the recent advances in the intestinal mucosal barrier along with the related bacterial infections, which may provide new ideas for scientific research, and clinical diagnosis and therapeutics.