The natural gas is extensively used in energy and chemical industries. The natural gas explosion accidents frequently occur in civil and industrial building closed space which are significantly different from gas explosions in a large length-width ratio tube. In current research, the effectiveness of the usage of N-2, CO2 and mixture of both suppressants in preventing and controlling gas explosion in a closed compartment is discussed. The thermal and reaction kinetics mechanisms involving inert gas suppression are discovered based upon the physical and chemical properties of both gases. The measurements of maximum explosion pressure, pressure rising rate and velocity of flame propagation are performed. The phenomena of fire core floatation and the "mushroom-shaped" flame in downward flame front are observed under the suppression of CO2 or mixture of N-2/CO2. The inhibiting effect of CO2 on CH4-air explosion is significantly better than that of N-2. The properties of physical heat absorption and chemical elementary reaction of both gases are analyzed to account for the difference of the explosion suppression effect. The findings of current research can provide basic data and theoretical guidance for inerting treatment or fire protection design of methane-air explosion in civil and industrial closed spaces.