Acrylamide bioaccessibility during and after in vitro gastrointestinal digestion of cereal and potato-based foods was monitored. Isolated vs combined meals were evaluated with the aim of investigating acrylamide-food matrix interactions. The meals considered were breakfast cereals, biscuits, patatas a lo pobre (patatas-pobre) and French fries for isolated foods; breakfast cereals with yoghurt, biscuits with milk, patatas-pobre with scrambled eggs and French fries with meat steak for combined foods. The non-bioaccessible fraction of acrylamide tended to decrease during the digestion process in all the systems. However, the final bioaccessible acrylamide was affected by the food matrix composition (fibre, protein, sugars and lipids). The digestion of breakfast cereals, biscuits with milk, patatas-pobre and patatas-pobre with scrambled eggs led to acrylamide bioaccessibility below the initial content of the contaminant in the meals. In absolute values, the combined consumption of biscuits and milk significantly reduced the bioaccessible acrylamide compared with isolated biscuits (from 212 to 122 ng; p < 0.05). The presence of protein sources (egg or meat steak) in the potato-based products significantly decreased the acrylamide bioaccessibility, which was more prominent in the French fries-meat steak system (from 2100 to 1698 ng; p < 0.05). These findings establish the importance of considering complete meals and not only isolated foods as well as the study of the non-bioaccessible fractions for a better understanding of acrylamide bioaccessibility, its recovery and interactions during gastrointestinal digestion.