For the first time, an electrochemical sensor was introduced by synthesizing a ZnO-Pd/Bi2O3 nanocomposite into a carbon paste electrode (CPE). The sensor was utilized to simultaneously measure both piroxicam (PIR) and naproxen (NAP). The synthesized nanocomposite’s characteristics were scrutinized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). Chronoamperometry, cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulse voltammetry (DPV) techniques were applied to study the electrochemical behavior of the modified electrode in aqueous solutions. A significant increase in the peak current response of PIR and NAP was observed with the ZnO-Pd/Bi2O3 nanocomposite modified carbon paste electrode (ZnO-Pd/Bi2O3/CPE) compared to the bare CPE. Through the DPV technique, ZnO-Pd/Bi2O3/CPE achieved the linear range of 0.3 to 1200 μM with the limit of detection (LOD) of 0.092 μM for PIR and the linear range of 0.5 to 900 μM with the LOD of 0.155 μM for NAP. Also, the limit of quantification (LOQ) for PIR and NAP has been calculated as 0.305 and 0.514 μM, respectively. The comprehensive analysis of real samples demonstrated the precise detection of PIR and NAP in wastewater, tablets, urine, and tap water, highlighting the broad applicability and reliability of the developed sensor in diverse real-world scenarios.