A peptide nanozyme was developed that mimics the dual antifungal actions of antimicrobial peptides (AMPs) and antimicrobial enzymes (AMEs). The nanozyme, named IHIHICI, was designed using a de novo approach with the help of AlphaFold2 and molecular dynamics simulations. The peptide was engineered to self-assemble into helical β-sheet nanotubes, which exhibit phospholipase C-like and peroxidase-like activities due to nickel coordination. These nanotubes demonstrate high thermostability and resistance to enzymatic degradation. The nanozyme effectively disrupts the cell wall and induces lipid peroxidation and ferroptotic death in Candida albicans, killing over 90% of the fungal cells within 10 minutes on a disinfection pad. The study highlights the potential of peptide-based nanozymes as an alternative to natural AMPs and AMEs, which are limited by poor stability and susceptibility to degradation. The developed nanozyme combines the advantages of both AMPs and AMEs, offering a dual mode of action that enhances antifungal efficacy. The nanozyme's unique structure and properties enable it to bind to fungal surfaces, disrupt cell walls, and induce oxidative stress, leading to microbial death. Additionally, the nanozyme shows high biocompatibility and minimal cytotoxicity, making it a promising candidate for clinical applications. The nanozyme's ability to target mannan in the fungal cell wall and disrupt membrane integrity demonstrates its effectiveness against a range of fungal pathogens, including Candida albicans and Gardnerella vaginalis. The study also shows that the nanozyme can be applied in practical settings, such as medical pads, where it effectively kills fungal cells within a short time. The results indicate that the de novo design strategy for peptide-based nanozymes can overcome the limitations of natural antimicrobial agents and provide a new approach for combating antimicrobial resistance.A peptide nanozyme was developed that mimics the dual antifungal actions of antimicrobial peptides (AMPs) and antimicrobial enzymes (AMEs). The nanozyme, named IHIHICI, was designed using a de novo approach with the help of AlphaFold2 and molecular dynamics simulations. The peptide was engineered to self-assemble into helical β-sheet nanotubes, which exhibit phospholipase C-like and peroxidase-like activities due to nickel coordination. These nanotubes demonstrate high thermostability and resistance to enzymatic degradation. The nanozyme effectively disrupts the cell wall and induces lipid peroxidation and ferroptotic death in Candida albicans, killing over 90% of the fungal cells within 10 minutes on a disinfection pad. The study highlights the potential of peptide-based nanozymes as an alternative to natural AMPs and AMEs, which are limited by poor stability and susceptibility to degradation. The developed nanozyme combines the advantages of both AMPs and AMEs, offering a dual mode of action that enhances antifungal efficacy. The nanozyme's unique structure and properties enable it to bind to fungal surfaces, disrupt cell walls, and induce oxidative stress, leading to microbial death. Additionally, the nanozyme shows high biocompatibility and minimal cytotoxicity, making it a promising candidate for clinical applications. The nanozyme's ability to target mannan in the fungal cell wall and disrupt membrane integrity demonstrates its effectiveness against a range of fungal pathogens, including Candida albicans and Gardnerella vaginalis. The study also shows that the nanozyme can be applied in practical settings, such as medical pads, where it effectively kills fungal cells within a short time. The results indicate that the de novo design strategy for peptide-based nanozymes can overcome the limitations of natural antimicrobial agents and provide a new approach for combating antimicrobial resistance.