Yeast extracts (YEs) are widely used by the food industry for the formulation of foods and beverages, as they bring a natural combination of flavour molecules, including aroma-active and non-volatile compounds (taste-active compounds). Adding a touch of umami, some richness or a typical flavour signature, YEs are used as ingredients to mask the bitterness of some food products. In the present work, using functional calcium mobilization assays, we demonstrated the ability of two different YEs (YE1 and YE2) and the ribonucleotide adenosine 5’ monophosphate (AMP) to stimulate heterologously expressed human bitter taste receptors named TAS2Rs. We then observed that YE1 inhibits the response of two TAS2Rs stimulated by control agonists. Our data demonstrate that the bitterness masking effect of YEs is a molecular mechanism occurring at the receptor level.