In this paper, a high-sensitivity electrochemical sensor based on platinum (Pt) doped nickel oxide (NiO) nanoparticles and multi-walled carbon nanotubes (MWCNTs) modified glassy carbon electrode (Pt-NiO/MWCNTs/GCE) has been developed to determine piroxicam (PIR) and amlodipine (AML) simultaneously. The electrochemical behavior of PIR and AML at the proposed sensor has been investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and chronoamperometry (CA) methods. Pt doped NiO nanoparticles were synthesized by the sol-gel procedure and were investigated using X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX) and field emission scanning electron microscopy (FESEM) techniques. DPV responses of PIR and AML increased linearly with their concentration in wide linear dynamic ranges of 0.6-320.0 μM and 1.0-250.0 μM, respectively. The limits of detection were 0.061 μM for PIR and 0.092 μM for AML. The excellent analytical figure of merits of the proposed modified electrode leads to application of it promising electrochemical sensor to determine PIR and AML in human serum and urine with satisfactory results.