Nanozymes are a new generation of artificial enzymes that utilize nanomaterials for biological catalysis. Discovered in 2007 by Yan and colleagues, who found that ferromagnetic nanoparticles exhibited peroxidase-like activity, nanozymes have since gained significant attention due to their high activity, stability, tunability, multifunctionality, and low cost for scale-up. Over the past 16 years, nanozymes have evolved into an interdisciplinary field, with over 420 laboratories from 42 countries reporting more than 1200 types of nanozymes and publishing over 10,000 papers. Nanozymes have shown comparable or better catalytic performance compared to natural enzymes and have potential applications in functional nanomaterials, biomedicine, new energy, green synthesis, and environmental treatment. This special issue features 25 papers, including reviews, perspectives, and research articles, covering topics from rational design and modulation to mechanisms and potential applications. Key contributions include the evolution of nanozyme definitions, reaction mechanisms, and the optimization of catalytic performance through machine learning, biosystem-inspired strategies, and surface engineering. Several nanozymes with specific applications are highlighted, such as those for treating traumatic brain injury, ischemic stroke, Down syndrome, and organophosphate toxins. The issue aims to accelerate the development of nanozymes and attract more researchers to explore their potential in various fields.Nanozymes are a new generation of artificial enzymes that utilize nanomaterials for biological catalysis. Discovered in 2007 by Yan and colleagues, who found that ferromagnetic nanoparticles exhibited peroxidase-like activity, nanozymes have since gained significant attention due to their high activity, stability, tunability, multifunctionality, and low cost for scale-up. Over the past 16 years, nanozymes have evolved into an interdisciplinary field, with over 420 laboratories from 42 countries reporting more than 1200 types of nanozymes and publishing over 10,000 papers. Nanozymes have shown comparable or better catalytic performance compared to natural enzymes and have potential applications in functional nanomaterials, biomedicine, new energy, green synthesis, and environmental treatment. This special issue features 25 papers, including reviews, perspectives, and research articles, covering topics from rational design and modulation to mechanisms and potential applications. Key contributions include the evolution of nanozyme definitions, reaction mechanisms, and the optimization of catalytic performance through machine learning, biosystem-inspired strategies, and surface engineering. Several nanozymes with specific applications are highlighted, such as those for treating traumatic brain injury, ischemic stroke, Down syndrome, and organophosphate toxins. The issue aims to accelerate the development of nanozymes and attract more researchers to explore their potential in various fields.