Electrophysiology is an indispensable tool in the early diagnosis of a wide range of diseases, making the precise, continuous, and stable recording of electrophysiological signals critically important. Organic electrochemical transistors stand out among various electrophysiological recording devices, offering a high signal-to-noise ratio due to their intrinsic amplification capability. However, despite their inherent advantages, several challenges persist in practical scenarios, such as the stability of wearable devices, limited spatiotemporal resolution, and undesired inter-channel crosstalk in implantable systems. Addressing these challenges may require innovative approaches in electrolyte engineering. This perspective summarizes the latest advancements and ongoing hurdles in the electrolyte engineering of organic electrochemical transistors, highlighting their potential to revolutionize advanced electrophysiological applications.