The development of tools for precisely recording neural chemical signals is crucial for understanding the dynamic chemical changes in the brain during physiological and pathological processes. Currently, in vivo electroanalysis based on implantable microelectrodes has become an important means for analyzing neural chemical signals in the brain. Among them, potentiometry, as one of the electrochemical methods, plays an important role in life science research due to its advantages such as miniaturized design, portability, low power consumption, and excellent neuronal compatibility. In recent years, the introduction of new sensing materials and the understanding of theoretical potential responses have enabled potentiometric biosensors to detect analytes of interest with high precision and sensitivity, ranging from non-electrochemically active substances such as ions to electrochemically active small molecules and even larger biomolecules. This article reviews the latest research progress of potentiometric sensors in brain sensing, including the response mechanism of potential and their applications in the field of in vivo analysis of brain neurochemistry.