General anesthesia is significantly gaining prominence and becoming unavoidable in modern medicine. Since neuroprotein fluctuations are common during anesthetic procedures, it is essential to monitor protein levels to identify neuro-related issues. Tau protein fluctuations are often found in the anesthetic process, and higher levels of tau are highly related to various neuro-related issues. Researchers are focusing on monitoring tau levels during and after anesthesia. This research has developed a high-sensitive tau biosensor on a gold nanomaterial-modified interdigitated electrode, measured at 0–2 V on a dual-probe station. Aptamer and antibody were used as capture and detection molecules, and a biotin-streptavidin strategy was employed to attach a higher number of aptamers on the electrode. These immobilized aptamers recognize the tau protein and form a sandwich with antibodies, lowering the detection of tau protein to 1 fM on a linear regression from 0.001 to 100 pM (y = 2.0651x - 1.3813, R2 = 0.987). Further, tau-spiked cerebrospinal fluid increases the current flow without any interferences, confirming the selective detection of tau protein.