Lost circulation prevention and plugging has always been a world-class problem troubling oil and gas drilling engineering, affecting the construction progress and causing economic losses. There are some problems of mismatch with the leakage channel, weak pressure capacity, and low success rate of primary plugging. Based on the dynamic reversible mechanism of disulfide bond, a chemical adhesive plugging agent with both mechanical properties and bonding properties is synthesized and evaluated. Chemical adhesive plugging agent has good dispersion and suspension stability in drilling fluid, and basically has no effect on the viscosity, shear force and filter loss of drilling fluid, and has good compatibility. The chemical adhesive plugging agent has the highest temperature resistance of 140 °C, and can be bonded into a whole after aging, sealing the pressure bearing capacity of 1–3 mm crack. By piling and bonding in the crack through the temperature and pressure response, the overall sealing layer formed has high pressure strength. The reduction rate of filter loss of sand disk reaches 53.53%, which has good sealing effect on microhole joint. The development of chemical adhesive plugging agent is of great significance for the efficient treatment of well leakage and the improvement of oil and gas drilling efficiency.