Purpose:Making orally disintegrating tablets and their active pharmaceutical ingredients palatable is one of the most significant technical obstacles to “patient friendly” formulations. Although flavor addition is widely used for taste masking, intense flavors may not be more appropriate for or accepted by all people. In this study, a new formulation using small peptides was tested for the taste masking of a very bitter tasting drug, Diphenhydramine. Methods: The low molecular weight poly(glutamic acid) (PGA) formed a specific complex with Diphenhydramine. The morphology of formed DPH/PGA complexes was studied using electronic scan miscroscopy (SEM). The physical and chemical properties of DPH/PGA complexes were characterized using an X-ray diffractometer, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and fourier transform infrared spectroscopy. Taste blocking efficiency of DPH/PGA complexes was examined using the Electronic Tongue. Results: Diphenhydramine formed complexes with PGA under acidic conditions trough a specific ionic interaction. Formed DPH/PGA complexes were mostly spherical in shape with a diameter of around 1.0 µm. These DPH/PGA complexes were stable at acidic pH (pH<3.0) but dissolved rapidly in weak acidic solution (pH=5.50) or under physiological conditions (pH=7.4). PGA complexation has proven to be as effective as sucralose for DPH taste blocking as tested using Electronic Tongue. Conclusion. The specific peptide formulation approach demonstrated in this study may solve the stability and dissolution problems of co-crystals and will have wide pharmaceutical applications, including drug delivery, taste masking, and enhancement of solubility.