Sepsis is a life-threatening disease caused by the dis-functioning of the immune response to pathogenic infections. Despite, the discovery of modern therapeutics and treatments of sepsis are lacking due to the resistance of pathogens. Metronidazole is an antibiotic commonly used to treat bacterial infections, but usage is limited and challenging by a short half-life period. In this research work, fabricate a pH-responsive drug delivery system for controlled release of metronidazole targeted molecules. We exemplified that, the encapsulation of hydrophilic metronidazole drug within a hydrophobic ZIF-90 framework can be enhanced the pH-responsive drug release under acidic conditions. The ZIF-90 frameworks only decompose in under acidic solutions, they are highly stable in physiological conditions. The pH-responsive protonation mechanism of ZIF-90 frameworks promotes the quick release of metronidazole within cells. The antimicrobial proficiency of zinc and metronidazole will expose a synergistic effect in ROS-mediated bacterial inhibition and auto-immunity boosting of normal cells. In vitro, antibacterial activity results revealed that the MI@ZIF-90 nano drug delivery system effectively eradicated human infectious pathogens at the lowest concentrations. In anti-fungal activity, studies show excellent growth inhibition against human pathogenic fungi Aspergillus fumigatus and Candida albicans. Finally, the PBMC cytocompatibility study concludes, that the fabricated MI@ZIF-90 drug delivery system is non-toxic to biomedical applications. The overall research findings highlight the design of a smart drug delivery system for sepsis treatment. In future it will be an efficient, low-cost, and biocompatible pharmaceutics for pediatric sepsis management processes.