Plagued with unpleasant aftertastes, bitterness, and mouth-puckering astringency, the utilization of sweeteners as regular sugar replacements has met with limited success. In this paper, we investigated mucin-sweetener interactions as a potential cause of the limitation of several popular sweeteners. We employed a QCM-D technique and rheological measurements to quantify the real-time interactions of Reb A, aspartame, sucralose, and sucrose with bovine submaxillary mucin (BSM) at normal oral pH of 7.0 and at pH 3.0, the average pH of typical carbonated beverages. At pH 7.0, the administration of sweetener solutions resulted in a subtle loss of the BSM layer. However, at pH 3.0, the injection of sweetener solutions caused an increase in adsorbed mass. Reb A's adsorbed mass was found to be the largest, 4-5 times that of sucrose and aspartame. The measured rheological properties suggest that the presence of sweeteners could cause a greater change in the BSM's elasticity and viscosity at pH 3.0, which could affect the sweetener-BSM interactions.