In this study, we aimed to enhance and accelerate the electrochemical properties of a glassy carbon-based voltammetric sensor electrode. This was achieved through the modification of the electrode using a nanocomposite derived from a metal–organic framework, which was embedded onto a substrate consisting of metal oxide nanoparticles. The final product was an electrocatalyst denoted as NiO/Ni@C-Fe3O4/CeO2, tailored for the detection of the drug niclosamide. Several techniques, including FT-IR, XRD, XPS, FE-SEM, TEM, and EDS, were employed to characterize the structure and morphology of this newly formed electroactive catalyst. Subsequently, the efficiency of this electrocatalyst was evaluated using cyclic voltammetry and electrochemical impedance spectroscopy techniques. Differential pulse voltammetry was also utilized to achieve heightened sensitivity and selectivity. A comprehensive exploration of key factors such as the catalyst quantity, optimal instrumental parameters, scan rate influence, and pH effect was undertaken, revealing a well-regulated reaction process. Furthermore, the sensor's analytical performance parameters were determined. This included establishing the linear detection range for the target compound within a specified concentration interval of 2.92 nM to 4.97 μM. The detection limit of 0.91 nM, repeatability of 3.1%, and reproducibility of 4.8% of the sensor were calculated, leading to the observation of favorable stability characteristics. Conclusively, the developed electrochemical sensor was successfully employed for the quantification of niclosamide in urine samples and niclosamide tablets. This application highlighted not only the sensor’s high selectivity but also the satisfactory and accurate outcomes obtained from these measurements.