Biomedicine and environmental research stand to gain significant advancements through the use of nanozymes. Researchers must examine safety and toxicity aspects related to biocompatibility before pursuing clinical or environmental applications of nanozymes. Nanozyme toxicity is determined by structure, size, surface charge, and composition, which together affect the way cells absorb these particles and how they distribute and clear from the body. Nanozymes smaller than 10 nanometers exhibit greater permeability compared to larger nanozymes but produce significantly more cytotoxic effects through excessive reactive oxygen species generation, mitochondrial damage, and resulting inflammation. Nanozymes created from metals consist of iron oxide and cerium oxide. The release of ions from these chemicals creates conditions that worsen oxidative stress and genotoxicity. Surface alterations, such as zwitterionic coatings and PEGylation, reduce immune evasion and toxicity, yet unresolved problems persist. Extended retention within the liver, spleen, and lungs generates concerns regarding the long-term effects on biocompatibility and exposure safety. Reactive oxygen species formation provides advantages in fighting bacteria and cancer but has the potential to cause accidental oxidative harm. The author notes a significant deficiency in standardized toxicity evaluations alongside biological interaction prediction models for biological systems. Biocompatible coatings, along with core-shell architectures and biodegradable materials, serve as engineering solutions to enhance safety and therapeutic effectiveness. Research focused on nanozymes’ molecular interactions remains essential to ensure their safe long-term application across medical, catalytic, and environmental fields.