CH4/DME mixtures can be used for engines and gas turbines, and have already been studied for many years. However, DME has a strong cool flame phenomenon, which will greatly influence the ignition and combustion characteristics of following hot flames. Therefore, the cool flame characteristics of CH4/DME mixture are very important for their utilization. Recently, the inhibition effect of CH4 on DME cool flames has been discovered, but the mechanisms of the inhibition effects lack further verification and research. In this study, the inhibition effects were investigated via both experiments and simulations. In order to validate the inhibition effects, a comparison fuel of CH3OH/DME was also used in this study. The extinction limits, flame temperatures and combustion products of the cool flames of the CH4/DME and CH3OH/DME mixtures were measured using a counterflow burner, and the reaction paths and heat release rate were derived from the HPMech-v3.3. The results indicate that CH4 and CH3OH will both inhibit the cool flame of DME via competing with DME for OH and O radicals, and CH3OH has stronger inhibition effects than CH4, because it is more competitive and produces more CH2O, which inhibits the oxidation of DME. The HPMech-v3.3 closely agrees with the experimental data, but still needs to be improved.