This is the first report to development of a new generation and highly sensitive electrochemical sensing platform based on gold nanoparticles/graphene/(AuNPs@GRP) nanocomposite for the detection of vortioxetine (VOR). The electrochemical behavior of VOR has been investigated through adsorptive stripping differential pulse voltammetry (AdsDPV) on the proposed electrochemical sensor (AuNPs@GRP/GCE). The structural and morphological characterizations of fabricated AuNPs@GRP composite were performed by x-ray diffraction (XRD) and transmission electron microscopy (TEM) methods. A well-defined and irreversible oxidation peak at 972 mV was observed on the surface of AuNPs@GRP/GCE. The proposed electrochemical sensor exhibited outstanding electrocatalytic activity towards the electroxidation of VOR. Under the optimized conditions, the voltammetric response was linearly proportional to VOR concentration at two working range of 0.1-1.0 and 1.0-6.0 mu M with a low detection limit of 50.0 nM. The developed sensor was successfully carried out for reliable determination of VOR in pharmaceutical sample with satisfying recovery results. AuNPs@GRP/GCE could be utilized as a simple, inexpensive and reliable sensing platform for the routine analysis of VOR as an antidepressant drug in pharmaceutical samples.