The gastrointestinal (GI) tract plays a critical role in nutrient absorption, immune responses, and overall health. Traditional models such as two-dimensional cell cultures have provided valuable insights but fail to replicate the dynamic and complex microenvironment of the human gut. Gut-on-a-chip platforms, which incorporate cells located in the gut into microfluidic devices that simulate peristaltic motion and fluid flow, represent a significant advancement in modeling GI physiology and diseases. This review discusses the evolution of gut-on-a-chip technology, from simple cellular mono-cultures models to more sophisticated systems incorporating bi-cultures and tri-cultures that enable studies of drug metabolism, disease modeling, and gut-microbiome interactions. Although challenges remain, including maintaining long-term cell viability and replicating immune responses, these platforms hold great potential for advancing personalized medicine and improving drug discovery efforts targeting gastrointestinal disorders.