The main compound found in galangal rhizome (Kaempferia galanga Linn.) Is Ethyl p-methoxy cinnamon (EPMS). EPMS can inhibit histamine release from mast cells by blocking IgE mediated signaling pathways. EPMS is thought to have antagonistic action against histamine receptors. The purpose of this study was to determine the effect on H1 receptors. Galangal rizome was extracted by maceration method using 96% ethanol solvent. The EPMS crystal which was identified using TLC, and GC-MS. In vitro tests were carried out on bath organs using isolated guinea pigs. EPMS is administered at levels of 100 μM and 200 μM. Known types of antagonisms of EPMS and EPMS levels can be given. In silico test of EPMS compounds against H1 receptors using AutoDock software. The results showed that the galangal rhizome contained EPMS based on TLC and GC-MS test results. Then EPMS was able to inhibit the tracheal contraction of guinea pigs induced by histamine agonists. The pD2 value at the H1 receptor has a significant difference at a dose of 200 μM (p <0.05) with the type of non-competitive antagonist seen from the shape of the contraction response curve that does not reach 100% Emax. The dose that can be given to inhibit tracheal smooth muscle contraction is 100 μM. The in silico test showed that the EPMS was able to bind to the H1 receptor (docking score: -3.90). EPMS binds to the amino acid Valine 187, which is an amino acid that binds with diphenhydramin. The conclusion of this study is the galangal rhizome contains EPMS and has activity as a non-competitive antagonist against H1 receptors.