Periodontitis, a chronic inflammatory disease affecting over one billion people worldwide, is characterized by bacterial infections and hyperactive immune responses. Recent studies have revealed that the formation of neutrophil extracellular traps (NETs) contributes significantly to periodontal tissue destruction, and NETs degradation plays a critical role in periodontitis treatment. Current treatments, including mechanical debridement and systemic antibiotics, face limitations such as antibiotic resistance and insufficient local efficacy. To integrate antibacterial and NETs-elimination strategies, the authors propose a novel therapeutic approach using bifunctional core-shell microneedles (MNs) that deliver two types of nanozymes: a peroxidase (POD)-like palladium (Pd) nanozyme in the inner core layer and a DNase-like dendritic mesoporous silica nanoparticles (DMSN)-cerium (Ce) nanozyme in the outer layer. The Pd/Ce MNs are designed to facilitate the rapid release of Pd for bacterial eradication and the sustained release of DMSN-Ce for NETs degradation. This study details the synthesis and characterization of two nanozymes and core-shell structured MNs, followed by evaluations of their catalytic activities, in vitro biocompatibility, antibacterial efficacy and NETs-cleavage ability. In vivo testing using a rat model of periodontitis demonstrates significant improvements in bacterial clearance, inflammation reduction, and alveolar bone preservation. In conclusion, these findings suggest that Pd/Ce MNs with superior antibacterial and NETs-hydrolyzing properties represent a promising therapeutic strategy for the management of periodontitis.