The cholecystokinin receptor-type 1 (CCK1R) is a G-protein coupled receptor localized in the animal gastrointestinal tract. Receptor activation by the natural peptide ligand CCK leads to a feeling of satiety. In this study, hydrolysates from soy and milk proteins were evaluated for their potential to activate the CCK1R, assuming that bioactive peptides with a satiogenic effect can be used as an effective therapeutic strategy for obesity. Different protein hydrolysates were screened with a cell-based bioassay, which relies on the generation of a fluorescent signal upon receptor activation. Fluorescence was monitored using a fluorescence plate reader and confocal microscopy. Results from the fluorescence plate reader were biased by background autofluorescence of the protein hydrolysate matrices, which makes the fluorescence plate reader inappropriate for the evaluation of complex formulations. Measurements with the confocal microscope resulted in reliable and specific results. The latter approach showed that the gastrointestinal digested 7S fraction of soy protein demonstrates CCK1R activity.