The present study correlates the polyphenolic composition of two different Nebbiolo red wines from the 2015 vintage (M and P), with the salivary proteins’ precipitation process. The work centered on the polyphenolic characterization of Nebbiolo wines and their interaction with different families of salivary proteins. Overall, both wines were found to be very reactive with human saliva which was supposed to contribute to their astringent character. The comparison of both wines showed that the M wine presented higher values of total phenolics, total proanthocyanidins, and tannin specific activity. Moreover, this wine showed a higher interaction with salivary proteins. Altogether, the chemical characterization and reactivity toward human saliva could contribute to the wine astringency.