Abstract Pharmaceutical compounds, such as ibuprofen and metoprolol, are of increasing concern due to their persistence in the environment and potential adverse effects on human health. In this work, we developed an electrochemical sensor system for the determination of ibuprofen and metoprolol based on a modified manganese oxide nanoparticle (MnO 2 NPs) on a screen‐printed carbon electrode (SPCE). The characterisation of MnO 2 NPs modifier was investigated via Fourier transform infrared (FTIR), X‐ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy techniques, Uv/vis spectroscopy, and small‐angle X‐ray scattering spectroscopy. The electrochemical behaviour of the MnO 2 NPs was studied using differential pulse voltammetry (DPV) and cyclic voltammetry (CV) techniques. The optimum experimental conditions were investigated by examining the effects of scan rates, pH on the CV responses, and electrolytes on the DPV response. The MnO 2 NPs modified electrode demonstrated enhanced catalytic activity in the electro‐oxidation of both ibuprofen and metoprolol. The oxidation peaks of ibuprofen and metoprolol were observed at +1.14 V and +1.46 V, respectively, for the MnO 2 NPs/SPCE sensor. The sensor's limit of detection was 3.81 pM and 4.6 pM respectively and its linear response was from 0.97–5.82 pM. Furthermore, interference and stability studies were conducted to evaluate the performance of the MnO 2 NPs/SPCE sensor under optimum conditions, which resulted in a good performance. The proposed sensor was successfully used for the determination of ibuprofen and metoprolol in the application of real water samples.