= 2.02 μM) with MrgprX2, representing the first quantitative assessment of this interaction. Molecular docking revealed four key binding residues (TRP248, ASP184, LEU247, and GLU164) that form stable interactions with fisetin. Pharmacological validation using LAD2 cells confirmed fisetin's potent anti-allergic activity via MrgprX2 antagonism. In summary, these findings not only identify fisetin as an active constituent of Rhus chinensis Mill but also further confirm that it targeted MrgprX2 to exert anti-inflammatory properties, offering new perspectives for developing anti-pseudoallergic therapeutics.