Astringency is a highly complex sensation which involves multiple mechanisms occurring simultaneously, such as the interaction between flavan-3-ols and salivary proteins (SP). Moreover, astringency development can be affected by the presence of polysaccharides such as mannoproteins (MP). The aim of this work was to evaluate the molecular mechanisms whereby MP could modulate the astringency elicited by tannins, using a cell-based model of the oral epithelium (TR146 cells), and the effect of salivary proteins on these interactions. The binding of flavan-3-ols to oral cells was evaluated by DMACA assay, while the content of unbound flavan-3-ols after the interactions was assessed by means of HPLC-DAD-MS. Results obtained confirm the existence of cell–tannin interactions, that can be partially inhibited by the presence of SP and/or MP. The most significant decrease was obtained in the system containing MPF (38.16%). Both mannoproteins assayed seem to have modulating effect on flavan-3-ol–SP interactions, acting by two different mechanisms: MPF would lead to the formation of SP/MPF/flavan-3-ols ternary soluble aggregates, while MPL seems to prevent flavan-3-ol–saliva interaction by a competitive mechanism, i.e., MPL would reduce cell–tannin interactions, similar to SP. This study suggests that mannoproteins with different compositional characteristics could exhibit preferential interaction with distinct flavan-3-ol families.