Abstract: In vitro digestion models enable precise quantification of the unique digestive behavior of whole grains and play a pivotal role in the development of coarse grain functional foods. By accurately characterizing their digestive properties and dynamic responses, these models have become an essential bridge linking the complex composition of whole grains to their health effects, thereby providing theoretical support for efficacy evaluation. To deepen the understanding of how in vitro digestion models contribute to functional food development and efficacy assessment, this review summarizes the functional and digestive characteristics of major components in whole grains—including starch, proteins, lipids, and phenolic compounds. It further highlights the principles, features, and practical applications of the two mainstream categories of in vitro digestion models, namely static and dynamic systems. Finally, through case studies involving formulation design, process optimization, and raw-material selection, the review elucidates the intrinsic connections between model applications and coarse grain properties, to provide references for the correlation analysis of in vitro-in vivo data and the precise design and development of coarse grain functional foods.