Abstract: Plant polyphenols were exploited in this research to reduce the antigenicity of β-lactoglobulin based on their mutual interaction (physical combination), in an effort to evaluate its potential on the application of new technics to fabricate hypoallergenic lactoproteins. In this study, non-covalent, alkaline, and enzymatic methods, were adopted to construct the complex or conjugated compounds of β-lactoglobulin combined by plant phenolic extracts from tea residue, mulberry pomace, longan pericarp, longan seed, grape seed and grape pomace. By means of the determination of allergenicity in vitro (through enzyme linked immunosorbent assay and immunoblotting), the six kind of plant polyphenols extracts could reduce the antigenicity (specific IgG binding capacity) of β-lactoglobulin to different extents (under alkaline and enzymatic treatment), in which longan pericarp and seed polyphenols exhibited the best (the mean of antigenic inhibition rate: 76.8%, 77.2%, respectively). Meanwhile, liquid chromatography coupled with tandem mass spectrometry indicated that gallic acid unit-based tannins (or acids), such as corilagin and ellagic acid, were dominant polyphenols in longan pericarp/seed extracts. In addition, gel electrophoresis revealed that six extracts induced aggregation between proteins, forming dimers or polymers. The solubility of the complexes or adducts constructed via enzymatic catalytic process was lower than the corresponding compounds built by non-covalent or alkaline methods (except for tea residue polyphenols group). Nonetheless, most of the extracts did not apparently affect the in vitro global digestibility of the protein, apart from the grape pomace treatment under alkaline condition. Taken the results of desensitization efficiency and functionality and digestibility into account, this study could preliminarily conclude that phenols stemmed from longan pericarp and seed might be the suitable materials in suppressing the allergenicity of β-lactoglobulin.