In order to solve the problem of working fluid loss during oil and gas drilling and production, a supramolecular gel plugging agent based on hydrophobic association was prepared by micellar copolymerization method in this paper, which can be used to plug fractures and pores in the formation during oil and gas drilling and production. The plugging agent is formed by free radical polymerization of acrylamide, octadecyl methacrylate, sodium dodecyl sulfate and other monomers. According to the requirements of plugging materials during oil and gas drilling and production, the forming time, rheology, swelling property, mechanical properties and plugging properties of supramolecular gels were evaluated in laboratory. The results show that the forming time of supramolecular gel plugging agent is controllable, and it has excellent viscoelastic recovery ability within a certain range of shear strain and scanning frequency. The compressive stress reaches 1.43MPa when the compression amount is close to 87%. Meanwhile, supramolecular gel has good swelling performance, and its swelling process is non-fickian diffusion type. Besides water molecular diffusion, the swelling process is affected by gel network and polymer chain relaxation, interaction between water molecules and polymer network and polymer network groups, etc. In addition, supramolecular gel has strong formation bonding ability, good plugging performance, plugging rate is greater than 95%, can effectively reduce leakage and improve the plugging effect of low and medium permeability gas reservoir, for the long-term plugging of heterogeneous and malignant gas loss, has reference and guiding significance.