This work reports on the analytical performance of carbon paste electrodes (CPE) modified with multi wall carbon nanotubes (MWCNT) and NiO nanoparticles for the determination of codeine. The morphology of Ni nanoparticles was investigated by scanning electron microscopy (SEM). Cyclic voltammetry and differential pulse voltammetry used for qualitative and quantitative electrochemical evaluation of codeine. Under the suitable conditions, the peak current increased linearly with the concentration of codeine in the range of 0.03 to 12.00 μM, with limits of detection (LOD) and the limits of quantitation (LOQ) 0.015 and 0.05 μM respectively. The proposed electrochemical sensor was successfully applied for quantifying codeine in various real samples includes Urine, Human serum, Codeine tablet.