In the drilling of shale formation, the problem of wellbore stability is relatively prominent. Due to the special physical and chemical properties of shale, it is easy to absorb water and expand, resulting in the wellbore falling and collapsing, so it is necessary to reinforce the wellbore during drilling. In this paper,the process of biomineralization is simulated to study the self-assembly technology of nanoparticles. Based on the selection of cationic polymers and nanoparticles, this paper focused on the self-assembly deposition process of modified calcium carbonate and BPEI, as well as the structural analysis of the deposition layer. The experimental results displayed that modified nano-calcium carbonate could form a well deposition layer on the simulated well wall. In addition, this paper also explored the application of this technique on the improvement of wellbore stability which would provide a new strategy to solve the problem of wellbore instability.