This study identified 9 derivatives of ferulic acid via in silico screening, aiming to explore the effect of molecular structure on bitterness inhibition. Their HepG2 cell LC50 values ranged from 0 to 1.65 mg/mL.The electronic tongue test results indicate that [3-(3-nitro-4,5-dihydroxyphenyl) acrylic acid] and [3-(2-chloro-4-fluorophenyl) acrylic acid] improved Acesulfame potassium bitterness inhibition by 21.18-27.35 %. [2-oxo-3-phenylpropionic acid] and [4-phenylbut-3-enoic acid] enhanced coffee bitterness suppression by 38.31-42.09 %. The absence of CC bonds in ferulic acid reduced inhibition, while nitro/phenol groups boosted suppression. Ferulic acid and its derivatives were found to form hydrogen bonds with residues R268 and Y241 in the TAS2R46 bitterness receptor, as identified by docking experiments (in silico), a critical condition for the bitterness suppression activity. These findings provide new insights for the development of bitterness inhibitors in the future.