Wheat flour, consisting of a complex matrix of starch and protein, is used as a representative model of whole food here to investigate the binary interaction in relation to amylose level and hydrothermal treatment in noodles as a food exemplar. Noodle made of high-amylose wheat (HAW) flour showed an eight-fold higher resistant starch content, compared to the wild type. Protein removal under simulated intestinal digestion conditions resulted in higher starch digestion rate coefficients in raw and cooked flours. In cooked flours, the substrate becomes similarly accessible to digestive enzymes regardless of protein removal. The results indicate that the increased protein content in native HAW flour and thermal stability of starch in HAW noodles lead to higher food integrity and consequently enhance the resistance against α-amylase digestion. Overall, the study suggests that a diversity of starch-protein interactions in wheat-based food products underlies the nutritional value of natural whole foods.