Porous silica particles have shown great potential application as reinforcing fillers in the field of dentistry due to their ability to construct the micromechanical interlocking effect at filler-matrix interface. However, how to accurately regulate the pore structure, especially the pore size, to increase the degree of the micromechanical interlocking and the performance of materials remains a challenge. Herein, we have proposed a facile self-assembly process to synthesize dendritic porous silica with tunable pore sizes (DPS-x) by adjusting the chain-length of the alcohols in the microemulsion. The mechanism of nucleation-growth is further put forward. The results indicate that the pore size of DPS-x indeed affects the mechanical property of composites, where the DPS-pen particles with intermediate pore size are chosen as the optimal reinforcing fillers. The bimodal and multimodal filler formulations are further established to address the loading limitation of unimodal DPS-pen (46 wt%). In virtue of the close-packed structure of identical spheres, the particle sizes of secondary silica embedded into the maximally loaded bimodal D3S7 composite (DPS-pen:Si430 = 30:70, wt/wt) are theoretically calculated without trials. Among all formulations, the developed multimodal D3S7+Si178+Si90 filler exhibits superior mechanical properties, the lowest shrinkage, and high polymerization conversion for dental composites, along with satisfied waster sorption and solubility, and good biocompatibility in vitro and in vivo, which are comparable to commercial composite Z350 XT (3M, USA). These DPS-x particles and their multimodal fillers can also be applied to other polymer-based biomaterials.