In this study, we report for the first time, a method for simultaneous detection of paracetamol (PA) and its toxic impurities, 4-aminophenol (4-AP), as well as commonly co-formulated drugs, ascorbic acid and zinc (AA and Zn (II)), using screen-printed electrodes (SPEs) as a sensing platform. To improve the electrochemical performance of the SPEs, these are decorated with platinum and nickel microstructures (Pt-Ni), using a simple electrode- position technique. The structures and morphologies of the synthesized Pt-Ni/SPE electrode were confirmed by FE-SEM, TEM, EDX, XRD and AFM measurements. Furthermore, electrochemical characterization of the as- prepared sensor was investigated using cyclic voltammetry and electrochemical impedance spectroscopy methods. Under optimum conditions, the content of 4-AP, PA, AA and Zn(II) was quantified using cyclic voltammetry, differential pulse voltammetry and square-wave voltammetry techniques. The designed sensor exploits a dual effect, leveraging the efficiency of Pt for Zn(II) detection and Pt-Ni for the detection of 4-AP, AA, and PA. On one hand the as-prepared Pt-Ni/SPE sensor exhibits a linear response towards 4-AP and PA, ranging from 0.5 to 200 mu M for both, with detection limits of 0.33 mu M and 0.23 mu M (S/N = 3) for 4-AP and PA, respectively. On the other hand, it demonstrates a linear response towards PA, AA, and Zn(II), ranging from 0.01 to 0.8 mu M for Zn(II), 10 to 1800 mu M for AA, and 0.5 to 200 mu M for PA, with detection limits of 0.004 mu M, 9.0 mu M, and 0.15 mu M for Zn(II), AA, and PA, respectively. Crucially, the as-fabricated sensor, with its remarkable reproducibility, recovery, long-term stability, and anti-interference capabilities, effectively quantified 4-AP, PA, Zn(II) and AA in both pharmaceutical formulations and human plasma samples.