Ethyl p-methoxy cinnamate (EPMC) is the second largest compound contained in Kaempferia galangal L., which is 31.36%. EPMC is reported to have an anti-diarrhea effect. Histamine receptors also play a role in stimulating smooth muscle and widening permeability, giving rise to the effects of vomiting and diarrhea. The purpose of this study was to determine the administration of EPMC from Kaempferia galangal L. against H1 histamine receptors and antagonism activity in isolated guinea pigs ileum and EPMC affinity values from the results of molecular docking. The maceration method is used to obtain Kaempferia galangal L extract, EPMC. EPMC was identified using TLC with the mobile phase toluene : ethyl acetate (19: 1). Antagonism activity test using isolated guinea pig ileum organ in vitro. Use of EPMS doses of 100 and 200 μM. Data obtained in the form of percent contraction of ileum which is converted into pD2 value. The pD2 value was statistically analyzed using One-way ANOVA then continued with the LSD test with a confidence level of 95%. The in silico assay of EPMC compounds on the H1 histamine receptor using AutoDock software. EPMS shows the antagonism activity of the H1 histamine receptor discussed by a decrease in the value of pD2 which is less than the value of pD2 when histamine agonists are induced. The pD2 EPMS value of smooth muscle contractions induced by agonists at doses of 100 and 200 μM reduced the decrease significantly (p <0.05). The EPMS affinity value from the molecular docking results for the H1 histamine receptor is -3.9