In the following study attempts were made to present a novel and sensitive strategy for sensing and determining sertraline. To reach the goal of the study therefore, nano-structured Ni(II)–LD (LD: levodopa) film was electropolymerized on glassy carbon electrode (GCE) which was modified by gold nanoparticles (Au NPs) enriched multi-walled carbon nanotubes (MWCNTs) in alkaline solution. Double-pulse electrochemical technique was applied for electrodeposition of Au NPs on MWCNTs which were immobilized on glassy carbon electrode surface. In the next step, the prepared Au NPs/MWCNT/GCE was modified with Ni (II)–LD film by using cyclic voltammetry technique. Structure of Ni (II)–LD/Au NPs/ MWCNT/GCE was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDX). Furthermore, the electrochemical behavior of Ni (II)–LD/Au NPs/MWCNTs composite and oxidation of sertraline in alkaline solutions was investigated by cyclic voltammetry (CV). It was found that the prepared Ni(II)–LD/Au NPs/MWCNTs nanocomposite, due to its unique properties, reveals high electrocatalytic activity towards oxidation of sertraline. Differential pulse voltammetry (DPV) was used for determining sertraline in the range of 0.05–5.5 mM with a good sensitivity (16.128 mA/mM) and a low detection limit of 95 nM (for S/N = 3). Finally, the developed sensor indicated several advantages, such as high stability, short time response and excellent reproducibility.