Central nervous system (CNS) disorders feature the progressive and selective loss of normal brain functions. CNS disorders often include an irreversible physiological and anatomical loss of neurons that can lead to dysfunction in various parts of the brain and eventually death. Glioblastoma multiforme (GBM) and neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are hard to be diagnosed at an early stage for the prevention of disease propagation. Such diagnosis is vital for the timely commencement of actual treatments. Nanotechnology brings new diagnosis hope for CNS disorders as it provides ultrasensitive detection for more specific biomarkers. This review summarizes the recent progress in techniques development for detecting pathological biomarkers for GBM, AD, and PD. In particular, the principles that govern the design of these sensors, blood-brain barrier (BBB) dysfunction, and its integrity during disease development. Finally, we present a perspective on future directions to further advance and improve the early-stage diagnosis of CNS disorders.