Efficient development of tight gas reservoirs is of great significance to alleviate energy security problems. Water plugging occurs during the development of tight sandstone gas reservoirs, which seriously affects the gas production of the reservoirs. However, the study on the effect of different chemicals on the water-locking behavior of tight sandstone gas reservoirs in situ is still lacking. In this study, wettability and permeability damage rate were characterized by contact Angle, and the influence of different agents on water lock phenomenon of tight sandstone gas reservoirs was discussed from the perspective of wettability change and water lock damage rate produced by different agents. It is found that in the wettability experiment, the initial contact Angle of the tight sandstone gas reservoir is 27.24°, and the hydrophilicity is strong. After soaking in the composite solution of surfactant and inhibitor, the contact Angle decreases, the hydrophilicity increases, and the water resistance intensifies. After soaking in the provided antiblocking agent, the contact Angle increases significantly, resulting in a decrease in hydrophilicity, which is conducive to the elimination of water blockage. After soaking in the modified agent, the change of contact Angle is not obvious, and the effect of water unlocking is not obvious. In the core displacement experiment, the core before and after displacement saturation was weighed to further verify that the wellbore agent retained the most in the core. The research results play an important role in determining the influence of different water plugging agents on water plugging of tight sandstone gas reservoirs, and help to effectively evaluate and select effective water plugging agents, so as to significantly increase the production of tight sandstone gas reservoirs.