Food industries are challenged to reformulate foods and beverages with higher protein contents to lower fat and sugar content. However, increasing protein concentration can reduce sensory acceptability due to astringency perception. Since the properties of food-saliva mixtures govern mouthfeel perception, understanding how saliva and protein interact is key to guide development of future protein-rich reformulations with optimal sensory attributes. Hence, this systematic review investigated protein-saliva interaction using both model and real human saliva, including a quality assessment. A literature search of five databases (Medline, Pubmed, Embase, Scopus and Web of Science) was undertaken covering the last 20 years, yielding 36 604 articles. Using pre-defined criteria, this was reduced to a set of 33 articles with bulk protein solutions (n = 17), protein-stabilized emulsions (n = 13) and protein-rich food systems (n = 4). Interaction of dairy proteins, lysozyme and gelatine with model or human saliva dominated the literature. The pH was shown to have a strong effect on electrostatic interaction of proteins with negatively-charged salivary mucins, with greater interactions occurring below the isoelectric point of proteins. The effect of protein concentration was unclear due to the limited range of concentrations being studied. Most studies employed a 1 : 1 w/w protein : saliva ratio, which is not representative of true oral conditions. The interaction between protein and saliva appears to affect mouthfeel through aggregation and increased friction. The searches identified a gap in research on plant proteins. Accurate simulation of in vivo oral conditions should clarify understanding of protein-saliva interaction and its influence on sensory perception.