The development of novel stimuli-responsive pesticide delivery systems is a highly effective strategy for improving pesticide utilization efficiency while minimizing environmental risks. A pH-, glutathione-, and chitinase-responsive pesticide delivery system (PYR@MONs-COS) was designed by conjugating chitosan oligosaccharide (COS) with biodegradable disulfide bond-bridged mesoporous silica nanoparticles (MONs) loaded with pyraclostrobin (PYR). The loading capacity of PYR in the nanoparticles was approximately 13.6%. The covalent attachment of COS to the modified MONs could effectively protect the active ingredient from photodegradation and prevent premature release of PYR. During the infection process, physiological and biochemical changes at the infection site, including reduced pH values, increased glutathione levels, and enhanced chitinase activity, facilitated the rapid degradation of disulfide bonds and COS in PYR@MONs-COS, resulting in the rapid release of PYR. Furthermore, PYR@MONs-COS significantly enhanced the foliar penetration of PYR, improved the adhesion of pesticide droplets, and stimulated callose deposition in rice leaves, thereby enhancing rice immunity. In antifungal activity assays, PYR@MONs-COS exhibited superior efficacy and prolonged efficacy against Magnaporthe oryzae compared to PYR microcapsules in both in vitro and in vivo experiments. The phytotoxicity assessment indicated that PYR@MONs-COS was safe for rice plants. More importantly, PYR@MONs-COS demonstrated a 7.3-fold reduction in acute toxicity to zebrafish compared to PYR technical. Therefore, the triple-stimuli pesticide delivery system has great potential for rice disease management and provides a promising pathway for the development of sustainable agriculture.