The remarkable lubrication provided by saliva in the oral cavity is vital to human health and wellbeing. Yet, molecular mechanisms for saliva lubrication remain unclear. In this work we report a possible mechanism of synergistic interaction between salivary proteins. By isolating a number of salivary protein fractions, we identify major protein candidates that contribute to saliva lubrication. We discover that a key driver for low friction is a hydrated brush-like layer formed by glycosylated species, with an essential synergistic contribution coming from the low molecular weight components that facilitate spreading, adsorption and strengthening of the salivary film on hydrophobic substrates. Lessons may be learned from saliva for understanding other natural bio-aqueous lubrication systems and for the development of saliva mimics.