Objective: Agonists for the bitter taste receptor T2R39 were explored. The activation regularities and molecular binding mechanisms of structurally different food-medicine homologous compounds on T2R39 were uncovered， and the inherent correlation between compound structure and receptor binding/activation was clarified. Combined with the physiological roles of T2R39 in metabolic regulation， intestinal homeostasis and dietary intervention， this study aimed to provide a theoretical basis for the development of T2R39-targeted functional foods and precise bitterness modulation. Methods: HEK293/Gα16-gust44 stable cells were used as the model， and T2R39 plasmid was transiently transfected with expression verified by Western blot. Calcium mobilization assay was performed to determine the activation effects and EC50 values of seven structurally representative food-medicine homologous compounds (myrcene， squalene， α-pinene， hesperidin， rutin， vanillin， succinic acid) screened in silico previously. Molecular docking was applied to analyze ligand-receptor binding modes and key interactions， and 100 ns molecular dynamics simulation was conducted to characterize conformational stability， hydrogen bond dynamics， residue flexibility and conformational remodeling of the complexes. Results: A specific band at approximately 38 ku was detected by Western blot， confirming successful expression of T2R39. Calcium flux indicated that succinic acid strongly activated T2R39 (EC50 = 4.15 nmol/L)， hesperidin and rutin exhibited potent activation (45-65 ΔF/F0)， α-pinene activated the receptor， myrcene and vanillin showed bell-shaped responses with inhibition at high concentrations， squalene displayed no obvious activation. Molecular docking and dynamics revealed that succinic acid activated T2R39 via an induced-fit mechanism， flavonoid glycosides maintained stable hydrogen-bonded conformations， and terpenoids bound through hydrophobic matching. Conclusion: T2R39 exhibited remarkable structure selectivity toward food-medicine homologous compounds， with hydrophobic interactions and hydrogen bond networks as the dominant binding forces. This study elucidated the structure-activity relationship of compound-receptor interactions and activation， laying a molecular foundation for the development of bitter taste receptor-targeted functional foods.