This is a study of the interactions between chitosan and mucin, the main oral/gastrointestinal thickener. Phase compatibility and separations were mapped between pH 1 and pH 7, where a region of strong phase separation exists upon co-existence of mucin and chitosan at about 2:1 wt ratios. No phase separations are discernible at lower pH values. -potential data suggest that electrostatic interactions between chitosan and mucin are expected only below pH 5. Fluorimetry data show that no direct bonds form between mucin and chitosan at pH 7, while strong associations arise from random and nonlocalized events, such as nonspecific dispersion (hydrophobic) associations leading to polymeric entanglements. At pH 3, two binding regimes exist, one at low chitosan concentrations involving both enthalpic and entropic interactions, and a second one at higher chitosan to mucin ratios, of purely enthalpic character, which is related to electrostatic and other direct interactions. A combination of oscillational and shear rheometry shows that, upon mucin addition, an inflexible chitosan coil conformation reverts into a shear-thinning, highly entangled polymeric network, which can be described by the fluorimetry data. The above results highlighted categorically that mucin (saliva) is directly involved in promoting the aggregation and/or fusion of chitosan-mucin complex.