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Brain diseases, including neurodegenerative disorders, brain tumors, and ischemic strokes, have shown significant threats to human neurological health and quality of life. With the aging population, the incidence of brain diseases continues to rise, further exacerbating public health issues. Traditional diagnostic methods, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), are hindered by limited image resolution and a high reliance on costly equipment. Single-molecule detection technologies, such as digital ELISA, have shown great promise for improving sensitivity, but their complex procedures and high costs remain barriers. Nanozymes, nanomaterials with enzyme-like activity, have emerged as a potential alternative. These materials offer high stability and lower costs in comparison with natural enzymes, making them ideal for portable, high-throughput diagnostics. In this review, we mainly summarize the types and applications of nanozymes with peroxidase-like activity and oxidase-like activity in brain disease biomarker detection and discuss the challenges and future directions for their clinical use.