Introduction: Numerous human studies have reported changes in the glycemic impact of potatoes due to cooking methods, suggesting differentiated starch digestion profiles. Cooking methods that affect cell wall integrity can influence nutrient accessibility and thereby digestibility. The aim of this work was to investigate these phenomena by studying the digestion of white and sweet potatoes. Methods: Raw white (Solanum Tuberosum) and sweet (Ipomoea batatas) potatoes were imaged using scanning electron microscopy. Following cell wall staining (calcofluor white) of raw, boiled and baked potato samples, cell wall integrity was assessed using confocal laser scanning microscopy. Semi-dynamic digestions of boiled and baked potatoes were carried out based on the standardized INFOGEST protocol. Digestion samples collected throughout oral, gastric and intestinal phases have been analysed to monitor the progression of protein and starch digestion. Results: In the raw white potato, starch granules appeared larger and separated from each other. Sweet potato presented smaller granules combined into clusters. After boiling, ruptured cell walls were visible in white potato and baking seemed to increase the level of damage. In contrast, most cell walls remained whole in cooked sweet potato samples. Starch and protein digestion progressed faster for white potato than sweet potato, regardless of the cooking method. Digestion was also overall faster after baking. Discussion: The differences in nutrient digestibility correlated well with the structural properties of each potato and the impact of cooking methods. The slower digestion profiles of sweet potato likely reflect the enhanced preservation of cell wall integrity after boiling and baking. Additionally, when comparing the effects of cooking methods on each food, increased cell wall damage through baking, was associated with higher overall digestibility. This study highlights the impact of cooking method on food microstructure and digestive profiles providing an explanatory framework that improves our understanding of human intervention studies.