The accumulation of bacteria at the margin of dental resin composites is the main reason for secondary caries, which may further cause failure of prosthodontics. Therefore, antibacterial activity is highly required. However, the addition of antibacterial agents or fillers weakens the mechanical or aesthetic properties of composites. In this work, regular-shaped SiO₂–ZnO complex clusters (CCs) constructed by spray-drying technology can enhance the antibacterial activity while maintaining the mechanical and aesthetic properties of dental resin composites. The results show that the regular shape and closely packed structure of nanoparticle clusters were not corrupted by the introduction of ZnO particles. As compared to resin composites filled with SiO₂ nanoparticle clusters, the comprehensive performances of composites containing SiO₂–ZnO CCs were further improved, and the composites filled with 70 wt% Si₆₆Zn₄ (CCs composed of 66/70 SiO₂ and 4/70 of ZnO) exhibited superior antibacterial capability (antibacterial ratio >99.9%) and acceptable depth of cure, degree of conversion, and biocompatibility. The cooperation of different fillers is highly essential for resin composites to achieve enhanced multifunctional performance.