Present study was undertaken to evaluate the anti-allergic activity of the ethanolic bark extract of Amoora cucullata (EBAC) in mice followed by molecular docking analysis and also to quantify the major bioactive polyphenolic constituents by HPLC analysis. Anti-allergic activity was evaluated using Toluene-2,4-diisocyanate (TDI)-sensitized allergy model mice by determining nasal allergy-like symptoms as well as counting the total and differential leukocytes profile of blood and Broncho Alveolar Lavage (BAL) fluid. In silico molecular docking study was performed using Schrödinger Maestro 10.1 on eight isolated compounds against Histamine Methyltransferase receptor in order to justify the anti-allergic activity of the extract. Acute toxicity test was performed to determine the safety of the extract. HPLC analysis exhibited the presence of 3,4-dihydroxy benzoic acid, catechol, (-) epicatechin, caffeic acid, syringic acid, rutin hydrate and trans-cinnamic acid. In anti-allergic activity test, oral administration of the EBAC improved nasal-allergic symptoms of TDI-induced allergic rhinitis in experimental mice. There was also a conspicuous decrease in the number of leukocytes, neutrophils, lymphocytes, eosinophils, monocytes and basophils in both blood and Broncho Alveolar Lavage (BAL) fluid of the mice treated with EBAC as compared to TDI-sensitized mice. Among the identified compounds from this plant, the docking score of Chrysin, Apigenin, Kaempferol-3-O-beta-D-glucopyranoside, and Stigmasterol against Histamine Methyltransferase receptor were comparable with that of standard drug Cetirizine (-9.519 kcal/mol). The EBAC did not exhibit any mortality in mice even at 3 gm/kg dose. The results of this study confirm the antiallergic activity of the plant in both in vivo and in silico investigations.