The complicated immunological mechanisms involved in hypersensitivity reactions are mediated by inflammatory pathways and cytokine signaling. The compounds made from natural plants present a possible substitute for controlling such reactions with fewer adverse results. This work aims to determine the antihypersensitive potential of bioactive phytochemicals found in the leaf extract of Eugenia caryophyllata (L.) Merr. & L.M. Perry by using an in silico method. The cyclooxygenase-2 (COX-2) (PDB ID: 3LN1) target proteins linked to hypersensitivity were chosen for molecular docking investigations. To evaluate the binding affinities and interaction patterns, phytoconstituents extracted (acetyleugenol, β-caryophylene, linalool, eugenol) from the Eugenia caryophyllata leaf extract were docked using AutoDock Vina. Additionally, SwissADME and Protox-II were used to assess ADMET analysis and drug-like features in pharmacokinetic behavior. The results showed that two bioactive compounds (acetyleugenol and eugenol) had good interaction patterns and high binding affinities (− 8.1 and − 7.3) with the target proteins, which showed a possible antihypersensitive effect. Additional in vitro and in vivo validation of the leaf extract as a natural treatment candidate for illnesses associated with hypersensitivity is made possible by this in silico investigation.