Carbon paste electrode modified with zinc oxide nano particles immobilized on multi-walled carbon nano tubes (MWCNTs/ZnO-NPs/CPE) was exploited for the simultaneous determination of Desvenlafaxine succinate (DVS) and Clonazepam (CLZ) in drug substance and combined drug products as well as in spiked human urine. The electrochemical response characteristics of the modified electrode toward DVS and CLZ were investigated by cyclic and differential pulse voltammetry (CV and DPV). The cyclic voltammograms showed well defined, irreversible cathodic peaks (reduction) at potential around -407 and -636 mV in Britton-Robinson (BR) buffer (pH 9.0) for DVS and CLZ, respectively. Different experimental factors affecting the method sensitivity have been investigated and optimized including pH of supporting electrolyte, electrode modifiers, different surfactant and scan rate. A good linear relationship was obtained between the peak current and the concentration within the range of 0.66-8.42 mu g/mL and 0.39-7.70 mu g/mL for DVS and CLZ, respectively using DPV method. The proposed method was successfully applied for the estimation of DVS and CLZ in its combined dosage form and in spiked human urine. The results obtained were validated according to ICH guideline and were found to be in agreement with those obtained by the reference HPLC methods. (C) 2018 The Electrochemical Society.