Developing radical oxygen species (ROS)-generating nanoreactors as new "antibiotics" is a promising strategy for the treatment of multidrug-resistant (MDR) biofilm infections. Herein, we designed and fabricated silver nanoparticle-decorated calcium peroxide (CaO2) nanoreactors (CPA) for combating MDR biofilms. CPA could locally boost ROS production as oxidative stress amplifiers in a pH-triggered and self-catalytic manner in acidic biofilms, where H2O2 was released by the hydrolysis of CaO2 and sequentially catalyzed by Ag NPs in situ to generate O2˙-, thereby efficiently disrupting mature biofilms and killing bacteria.