Physiological functions of the two extreme ends of the age spectrum, children (<18 y old) and older adults (aged 65 y and over), differ from healthy young adults. This consequently affects the pharmacokinetic profiles of administered drugs, which, in turn, impacts upon clinical practice and drug therapy. The gastrointestinal milieu acts as a distinct and vital organ regulating the dissolution, absorption and metabolism of orally ingested drugs. Age-mediated alteration in the physiology and function of the gut can reshape the pharmacokinetics of certain drugs. However, our understanding of this topic is limited. This article references the gut physiology of healthy adults to capture the available evidence in the literature on the extent and nature of the changes in childhood and older age. The gut, as an organ, is examined with regards to the effect of age on luminal fluid, microbiota, transit and motility, and the intestinal mucosa. Whilst drastic developmental changes were observed in certain aspects of the gastrointestinal environment, the examination reveals significant gaps in our knowledge in the physiology and function of the developing or ageing gut. The revelation of the unknown paves the way towards a better characterization of the human gastrointestinal tract for optimized drug therapy in children and older adults.