<p>Nowadays, bacterial infections pose a threat to human health. Wound infections not only have an impact on individual health, but they also raise the cost of medical care and public health threats, and there is no specific approach for treating bacterial wound infections. Ganoderic Acid A (GA.A) is a naturally occurring triterpenoid with powerful anti-inflammatory and antioxidant activities. Zeolitic imidazolate framework-8 (ZIF-8) has intrinsic antimicrobial capabilities, which are primarily due to its constituents: antimicrobial imidazole chemical ligands and physiologically active Zn²⁺. In the current study, we synthesized the complex antibacterial agent ZIF-8@GA.A at room temperature, and the success of the synthesis was demonstrated by infrared spectroscopy, ultraviolet–visible spectroscopy, X-ray diffraction, scanning electron microscope, transmission electron microscope. In vitro experiments were performed to determine the bacterial viability of <i>Escherichia coli</i> (<i>E. coli</i>) using the co-culture method, and the complex antibacterial agent ZIF-8@GA.A&#xa0;showed significant growth inhibition against <i>E. coli</i>. In vivo experiment, the ZIF-8@GA.A modulates inflammatory responses through down-regulation of IL-1β expression while enhancing phagocytic activity by upregulating CD11b in macrophages and neutrophils, thereby facilitating bacterial clearance and cellular debris removal. Furthermore, it promotes vascular endothelial cell proliferation and migration via upregulation of CD31 gene expression, ultimately accelerating angiogenesis and tissue repair processes. This new complex antibacterial agent ZIF-8@GA.A has great potential in treating wound infections.</p>