Biofilms are associated with many infectious diseases in humans, including those occurring in the mouth.Biofilm consists of microbial cells that are firmly attached to a surface and enmeshed in a 3D extracellular matrix of nucleic acids, proteins and polysaccharides, which protect resident bacteria from external biocide while promoting drug resistance.Thus, biofilms are difficult to remove and the resident microorganisms frequently become recalcitrant to antimicrobial therapies.Hydrogen peroxide (H2O2) is a "green chemical" that has various cleaning and disinfectant uses.However, its efficacy is limited against biofilm-forming bacteria, because of poor penetration into the protective, organic matrix.Nanozyme that could catalyze H2O2 to generate free radicals might have great utility for biofilm prevention or disruption.Here we developed a novel strategy for biofilm control using iron oxide (Fe3O4) nanozyme with peroxidaselike activity in potentiating the efficacy of H2O2.Biofilms formed from Pseudomonas aeruginosa (wound biofilm) and Streptococcus mutans (oral biofilm) were challenged with iron oxide nanozyme-H2O2 system and the efficiency for biofilm disruption and resident bacteria killing were evaluated by analyzing the biomass and cell viability.The enhanced cleavage of biofilm components (nucleic acids, proteins, and polysaccharides) was investigated to understand the mechanism of biofilm disruption by iron oxide nanozyme-H2O2 system.We found that the iron oxide nanozyme efficiently broke down the existing biofilm and prevented new biofilms from forming, killing both planktonic bacteria and those within the biofilm.The effective biofilm disruption is attributed to the intrinsic peroxidase-like activity of iron oxide nanozyme which enhanced bacterial killing via generation of free-radicals from H2O2 while also cleaving nucleic acids, proteins and polysaccharides that are present in the biofilm matrix.Our data show that iron oxide nanozyme could be a promising new approach for controlling biofilm formation by enhancing the bioactivity of a common and readily available antimicrobial agent.