The coupling effect of the side explosion vent and wire mesh on suppressing methane explosion has been investigated in this study, aiming to prevent huge losses caused by a methane explosion in industrial organic waste gas treatment. It constructed a closed simulation duct with a length of 3000 mm and an internal dimension of 120 mm × 120 mm containing a side explosion vent at different positions, in which flame behaviours and overpressure characteristics accompanying methane explosion were analyzed to get conclusions. The results indicate that side explosion vents located in the same duct section have a similar explosive flame development trend, and the suppression effect is better as closer to the ignition source. Besides, it is necessary to avoid the redevelopment of flame and the backfire downstream of a side explosion vent. In addition, the overpressure released through side explosion vents is significantly suppressed. However, the wave-absorbing and heat-absorbing properties of the wire mesh installed in the duct are only effective for some configurations with low flame speeds. Moreover, the side explosion vent closed to the ignition source effectively suppresses undeveloped flame. In this case, it leads to a complete application of the porous media quenching performance. To sum up, the coupling suppression effect of the side explosion vent and wire mesh on flame is complementary. However, there is an opposite conclusion for the experimental configurations where side explosion vents are downstream of the duct; a high-speed turbulent flame is difficult to be suppressed by the wire mesh and side explosion vent in a flame acceleration mechanism.