The aim of this study is to examine the response of Pinctada maxima shell to drilling predation, focusing on the underlying protective mechanisms. The shell exhibits a self-assembled smart architecture with a highly multilayered structure. The outer layer is composed of a prismatic structure, and the inner nacreous layer consists of several sub-layers that contain normal brick-like platelets and unique convex lens-like platelets, with myostracal layers laying in between them. Such a smart architecture provides several fundamental protective mechanisms against drilling penetration. First, the occurrence of multiple microcracking and the deformability of platelets in the nacre structure with brick-like platelets can effectively lock the damage locally during drilling penetration. Second, a few myostracal layers embedded within the nacre structure as a disguise of fresh body may induce the driller to inject the toxic salivary secretions, thus protecting the platelets at the bottom of the hole. Third, a new type of platelets with a convex lens-like shape is observed for the first time to be positioned in the internal part of the shell. This layer can effectively prevent the final attack due to its remarkable plastic deformation capacity or bendability via converting a part of tensile stresses into compressive stresses through interfacial sliding and rotation among the convex lens-like platelets. The findings of the present study can pave the way for the development of bioinspired advanced engineering structures with superior protectability against the penetration.