In this study, a new nanocomposite consists of magnetic graphene oxide (GO/FeO), poly-methyldopa (PMDA) and Pd nanoparticle was prepared and utilized for constructing an electrochemical sensor to determine acetaminophen (AC) and phenylephrine (PHE). The structure of nanocomposite has been characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX). The effects of various parameters with effective on the sensor response are optimized. In a range, 5 nM to 2.5 μM for AC and 50 nM to 3 μM for PHE the designed sensor had a response linearly reliant on the AC and PHE concentration respectively by differential pulse voltammetry. Also, the limits of detection for AC and PHE with this sensor were 2.1 nM and 7.8 nM, respectively. It successfully employed for the determination of trace amounts of the AC and PHE in pharmaceutical combination and human serum samples.