Airborne pathogens severely threaten public health worldwide. Air disinfection is essential to ensure public health. However, excessive use of disinfectants may endanger environmental and ecological security due to the residual disinfectants and their by-products. This study systematically evaluated disinfection efficiency, induction of multidrug resistance, and the underlying mechanisms of disinfectants (NaClO and H2O2) on airborne bacteria. The results showed that airborne bacteria were effectively inactivated by atomized NaClO (>160μg/L) and H2O2 (>320μg/L) after 15min. However, some bacteria still survived after disinfection by atomized NaClO (0-80μg/L) and H2O2 (0-160μg/L), and they exhibited significant increases in antibiotic resistance. The whole-genome sequencing of the resistant bacteria revealed distinct mutations that were responsible for both antibiotic resistance and virulence. This study also provided evidences and insights into possible mechanisms underlying the induction of antibiotic resistance by air disinfection, which involved intracellular reactive oxygen species formation, oxidative stress responses, alterations in bacterial membranes, activation of efflux pumps, and the thickening of biofilms. The present results also shed light on the role of air disinfection in inducing antibiotic resistance, which could be a crucial factor contributing to the global spread of antibiotic resistance through the air. Environmental implicationsOxidative disinfectants, such as sodium hypochlorite (NaClO) and hydrogen peroxide (H2O2), are widely used to ensure public health. However, excessive use of disinfectants may endanger environmental and ecological security due to the residual disinfectants and their by-products. This study evaluated the disinfection efficiency of atomized NaClO and H2O2, investigated the induction of antibiotic resistance, and also explored the underlying mechanism. This study can draw public attention to the excessive use of disinfectants, and provide evidence and suggestions for rational use of disinfectants.