In this paper, immunosensors based on a self-assembly modified (SAM) Au electrode for the specific detection of two illicit drugs, morphine (MO) and methamphetamine (MA), are reported. Using 3-mercaptopropionic acid SAM and activation by 1-ethyl-3-(3-dimethylaminoprophyl) carbodiimide (EDC)/n-hydroxysulfsuccinimide (NHS) with an adequate quantity of the antibody of MO or MA immobilized onto the surface to act as the sensing host, the sensors specifically respond to their respective target based on specific covalent bonding. Electrochemical impedance spectroscopy (EIS) is used as the read-out signal. The value of the electron transfer resistance (R-et) responded to the concentration of drug in spiked blood samples with an ultra-low detection limit and satisfactory recovery. In conclusion, the developed sensors are demonstrated to be more advantageous compared to those previously reported in terms of sensitivity. (C) 2014 Elsevier B.V. All rights reserved.