Y It is crucial to replicate or mimic the human digestive system conditions closely in model systems to have the food digestion-related data as accurate as possible. Thus, the data obtained could contribute to studies like those on the relationship between health and nutrition. This review aims to express the human digestion system's role in food digestion and compare the capability of the models used in simulations, especially the dynamic in vitro models. Activities of the human digestive system governing food digestion and the food matrix's disintegration mechanism in the digestive system were discussed. Dynamic in vitro models and their relevance to the human digestive system were described. Advancements in the last 20 years, as well as limitations of those artificial systems, with prospects, were discussed. Extensive use and improvement on these models will extend our knowledge of the food matrix and digestive system's complex interaction. Thus, it will be possible to design next-generation foods with improved health benefits.