The nanoscale pores in shale oil and gas are often filled with external nanomaterials to enhance wellbore stability and improve energy production. And there has been considerable research on discrete element blocking models and simulations related to nanoparticles. In this paper, the pressure transmission experimental platform is used to systematically study the influence law of different water activity salt solutions on shale permeability and borehole stability. In addition, the force model of the particles in the pore space is reconstructed to study the blocking law of the particle parameters and fluid physical properties on the shale pore space based on the discrete element hydrodynamic model. However, the migration and sealing patterns of nanomaterials in shale pores are unknown, as are the effects of changes in particle parameters on nanoscale sealing. The results show that: (1) The salt solution adopts a formate system, and the salt solution is most capable of blocking the pressure transmission in the shale pores when the water activity is 0.092. The drilling fluid does not easily penetrate into the shale pore space, and it is more capable of maintaining the stability of the shale wellbore. (2) For the physical blocking numerical simulation, the nanoparticle concentration is the most critical factor affecting the shale pore blocking efficiency. Particle size has a large impact on the blocking efficiency of shale pores. The particle diameter increases by 30% and the pore-blocking efficiency increases by 13% when the maximum particle size is smaller than the pore exit. (3) Particle density has a small effect on the final sealing effect of pore space. The pore-plugging efficiency is only increased by 4% as the particle density is increased by 60%. (4) Fluid viscosity has a significant effect on shale pore plugging. The increase in viscosity at a nanoparticle concentration of 1 wt% significantly improves the sealing effectiveness, specifically, the sealing efficiency of the 5 mPa-s nanoparticle solution is 16% higher than that of the 1 mPa-s nanoparticle solution. Finally, we present a technical basis for the selection of a water-based drilling fluid system for long horizontal shale gas drilling.