In the present research, a glassy carbon electrode (GCE) was activated aided by an electrochemical process in a 0.5 molar sodium hydroxide solution and then modified by nickel oxide (NiO) nanoparticles and multiwall carbon nanotubes (MWCNT) to obtain NiO/MWCNT/OGCE electrode. This electrode was morphologically and structurally characterized by scanning electron microscopy and electrochemical impedance spectroscopy. Cyclic voltammetric and chronoamperometry methods were employed to investigate the catalytic properties of the modified electrodes for Alfu electro-oxidation in buffer solution. The modified electrode exhibited promising electrocatalytic properties toward the oxidation of Alfuzosin (Alfu). The electrocatalytic role of NiO in Alfu electro-oxidation process was clearly demonstrated in comparison to the OGCE/MWCNT electrode. The reason behind this electrocatalytic activity relays on a synergistic effect involving both NiO and MWCNT. Differential pulse voltammetry (DPV) was employed as a sensitive procedure for the quantitative determination of Alfu. It was found that the oxidation current is in direct relationship with the concentration of Alfu in the 0.01-2.0 mu M and 2.0-90 mu M concentration ranges, with 0.0006 mu M detection limits. Moreover, no significant response was observed in the presence of the common interference, demonstrating the good selectivity of Alfu. The method was successfully used for the determination of Alfu content in real samples. (C) 2019 The Electrochemical Society.