Protein structure influences the accessibility of enzymes for digestion. The proportion of intramolecular β-sheets in the secondary structure of native proteins has been related to a decrease in protein digestibility. Changes to proteins that can be considered positive (for example, denaturation and random coil formation) or negative (for example, aggregation and Maillard reactions) for protein digestibility can occur simultaneously during processing. The final result of these changes on digestibility seems to be a counterbalance of the occurrence of each phenomenon. Occurrence of each phenomenon depends on the conditions applied, but also on the source and type of the protein that is processed. The correlation between denaturation enthalpy after processing and protein digestibility seems to be dependent on the protein source. Heat seems to be the processing parameter with the largest influence on changes in the structure of proteins. The effect of moisture is usually limited to the simultaneous application of heat, but increasing level of moisture during processing usually increases structural changes in proteins. The effect of shear on protein structure is commonly studied using extrusion, although the multifactorial essence of this technology does not allow disentanglement of the separate effects of each processing parameter (for example, heat, shear, moisture). Although most of the available literature on the processing of feed ingredients reports effects on protein digestibility, the mechanisms that explain these effects are usually lacking. Clarifying these mechanisms could aid in the prediction of the nutritional consequences of processing conditions.