After COVID-19 pandemic, Mucormycosis (black fungus) spreads as one of its related complications, due to the decrease in immunity system after administration of COVID-19 treatment drugs. A combination therapy of Itraconazole (ITR) and Terbinafine (TEB) was proved to be effective for treatment of black fungus. A novel electrochemical sensor was designed for estimation of ITR & TEB simultaneously by square wave voltammetric (SWV) technique. The sensor was fabricated using N&S-codoped magnetic quantum dots (N,S-MQDs) and ruthenium nanoparticles (Ru NPs). The fabricated sensor was characterized by cyclic voltammetry (CV), scanning electron microscope (SEM), powder X ray diffraction (pXRD), Fourier transform-Infrared (FT-IR), Raman spectroscopy and electrochemical impedance spectroscopy (EIS). Full optimization study for various experimental and instrumental parameters, in addition to method validation following International conference on Harmonization (ICH) guidelines was achieved. A good linearity in the range of 0.5–30 μg mL− 1 with limit of detection (LOD) 0.24 and 0.19 μg mL− 1 for ITR and TEB, respectively were obtained. The sensor was applied for analysis of ITR and TEB simultaneously in human plasma and urine samples without any interferences by applying dispersive magnetic solid phase micro-extraction (dMSPE) technique, where excellent recovery results exceeding 95 % were achieved