Nanozymes are increasingly being explored for oral therapy because their catalytic activity can serve two seemingly opposing purposes: generating reactive oxygen species (ROS) to disrupt pathogenic biofilms or removing excess ROS to protect inflamed and damaged tissues. However, their therapeutic performance depends on factors beyond catalytic activity measured under ideal experimental conditions. Oral disease sites differ markedly in pH, oxygen availability, substrate concentration, biofilm structure, and salivary exposure, all of which can influence catalytic reactions and local material retention. This review examines oral nanozymes in the context of their interactions with material properties and disease pathophysiology. We first discuss the major nanozyme platforms, their enzymelike activities, and structural factors governing catalytic performance. We then consider their application in dental caries, periodontal and peri-implant diseases, salivary gland dysfunction and xerostomia, and oral ulceration. Across these conditions, therapeutic strategies range from acid-enhanced catalytic biofilm disruption and oxygen-generating decontamination to antioxidant regulation of inflammatory tissue environments and localized mucosal delivery. Particular attention is given to how morphology, oxidation state, surface defects, and delivery systems influence the catalytic activity ultimately expressed at the lesion. Finally, we examine the remaining barriers to translation, including dependence on exogenous H2O2, limited lesion retention, inconsistent approaches to catalytic characterization, incomplete preclinical models, oral-specific safety concerns, and manufacturing reproducibility. Rather than simply maximizing catalytic activity alone, future oral nanozyme design will require matching a reproducible catalytic function to the biological and physicochemical conditions of the target disease.

Introduction
Nanozymes for Oral Applications
    1. Types of nanozymes
    2. Enzyme-like activities
    3. Determinants of catalytic activity
    4. Catalytic behavior and delivery in oral diseasemicroenvironments
Nanozyme-based Treatment of OralDiseases
    1. Dental caries
    2. Periodontal and peri-implant diseases
    3. Salivary gland dysfunction and xerostomia
    4. Oral ulcers
Challenges and Future Perspectives
    1. Dependence on exogenous H2O2
    2. Material bias and function/composition relationships
    3. Delivery, retention, and lesion-selective activation
    4. Limitations in preclinical evidence andstandardization of catalytic activity
    5. Oral-specific safety considerations
    6. Clinical translation and manufacturing reproducibility
Conclusion
Funding
Conflict of interest
References

• Youngjoon Kim(Department of Physiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea)
• Sang-woo Lee(Department of Physiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea) Corresponding author