The gut is a vital organ that is central to the absorption and metabolic processing of orally administered drugs. While there have been many models developed with the goal of studying the absorption of drugs in the gut, these models fail to adequately recapitulate the diverse, complex gastrointestinal microenvironment. The recent emergence of microfluidic organ-on-a-chip technologies has provided a novel means of modeling the gut, yielding radical new insights into the structure of the gut and the mechanisms through which it shapes disease, with key implications for biomedical developmental efforts. Such organ-on-a-chip technologies have been demonstrated to exhibit greater cost-effectiveness, fewer ethical concerns, and a better ability to address inter-species differences in traditional animal models in the context of drug development. The present review offers an overview of recent developments in the reconstruction of gut structure and function in vitro using microfluidic gut-on-a-chip (GOC) systems, together with a discussion of the potential applications of these platforms in the context of drug development and the challenges and future prospects associated with this technology. STATEMENT OF SIGNIFICANCE: This paper outlines the characteristics of the different cell types most frequently used to construct microfluidic gut-on-a-chip models and the microfluidic devices employed for the study of drug absorption. And the applications of gut-related multichip coupling and disease modelling in the context of drug development is systematically reviewed. With the detailed summarization of microfluidic chip-based gut models and discussion of the prospective directions for practical application, this review will provide insights to the innovative design and application of microfluidic gut-on-a-chip for drug development.