Current antibacterial sprays face major limitations, including rapid evaporation, short-lived efficacy, skin irritation, and poor adhesion to surfaces, highlighting an urgent need for a durable and biocompatible alternative. To address these challenges, we developed a ZIF-8-based spray (ZNS-WO20) composed of ZIF-8 nanoparticles dispersed in 50% ethanol and 20% OTES. OTES acts as a dispersant and binder, enabling wash-resistant coatings on gauze and glass. ZIF-8 exhibits pH-responsive Zn²⁺ release, achieving nearly 100% killing of S. aureus, E. coli, and methicillin-resistant S. aureus (MRSA) at 160 μg/mL through intracellular reactive oxygen species (ROS) generation. The spray maintains >95% antibacterial efficacy against S. aureus after five washing cycles and seven days of outdoor exposure, and causes no dermal irritation in rats. This work fills the gap for a long-lasting, skin-friendly antibacterial spray, showing promise for healthcare disinfection and surface protection.