Despite the increasing attention to food digestion research, food scientists still need to better understand the underlying mechanisms of digestion. Most in vitro studies on protein digestion are based on experiments with protein solutions. In this study, the digestion of egg white protein and whey protein isolate in solution and in gels was investigated using simulated gastric conditions. The digestion process was followed via the dry matter loss, degree of hydrolysis and peptide distribution. We showed that the performance of pepsin is an important factor in protein digestion, and hydrodynamic force effectively disintegrated the gel particles and enhance the hydrolysis of protein. The gel microstructure had shown to be a hindrance for the digestion of protein. However, the hindrance is not simply slowing down the hydrolysis, but also altering the apparent enzyme kinetics to some extent: while the dissolved proteins were hydrolysed through a ‘zipper’ type mechanism, the gels showed a slower ‘one-by-one’ mechanism. Overall, we believe that the digestion of the protein gels is influenced by the microstructure of food matrices, caused by the immobilisation of the substrate in the network, and the steric hindrance in the diffusive ingression of pepsin and egression of peptides.