Hydrophilic drugs are one of the most challenges in biopharmaceutical research. Hydrophilic drugs show low bioavailability following oral administration because of their poor intestinal permeation. This review sets out to discuss about anatomy and physiology of the intestinal barrier, drug absorption from intestinal tract, mechanism of intestinal drug permeability, detail information about intestinal permeation enhancers and its mechanism of action, in-vitro methods for studying drug permeability, advantages and applications of intestinal permeation enhancers.