In this research paper, an innovative electrochemical sensor was suggested for simultaneous voltammetric analysis of azithromycin (AZM) and hydroxychloroquine (HCQ) for the first time. The sensor based on hydrothermal synthesis of vanadium disulfide quantum dots (VS2 QDs) and insertion within 3D N, S graphene aerogel (3D N, S @ GNA) and carbon nanotubes nanaostructure as a new and widely group of carbon nanomaterials. The nanocomposites were characterized morphologically using different techniques. In addition, the nanomaterials were characterized electrochemically using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). The proposed electrochemical sensor showed wide dynamic linear ranges of 0.28–30 × 10−8 M and 0.84–22.5 × 10−8 M for analysis of AZM and HCQ, respectively. The limits of detection (LODs) based on signal to noise (S/N) 3:1 were found to be 0.091 × 10−8 M and 0.277 × 10−8 M for AZM and HCQ, respectively. Briefly, the electrochemical sensor had good stability, selectivity, reproducibility and feasibility for simultaneous detection of AZM and HCQ in presence of different interfering species.