The study describes a new approach for the direct electro-oxidation of captopril (CAP) drug using a CuO modified ITO electrode. The modified ITO electrode consists of an in situ grown film which accommodates dense CuO nanostructures with morphological features similar to flowers. The in situ growth over the ITO substrate was achieved using a simple hydrothermal route with the assistance of malonic acid which acted as an effective growth template. The devised electrode was evaluated in reference to its slurry-derived counterpart which involved surface modification of GCE using a conventional approach (drop-casting). The competitive evaluation of the discussed electrodes against the electro-oxidation of CAP, provided significant evidence to support the importance of controlled nanostructure distribution over the electrode surface to achieve higher signal sensitivity and reproducibility. The devised ITO/CuO electrode was known to possess excellent sensing capability against CAP within the linear working range of 0.01 to 3.43 mu M with signal sensitivity down to 2 x 10(-3) mM. Moreover, the ITO/CuO was noted to exhibit high charge transfer co-efficient (a), diffusion coefficient (D) and rate constant values of 0.83, 9.28 x 10(-5) cm(2) s(-1) and 3.5 x 10(3) mol(-1) L s(-1) respectively. In addition, the successful usage of ITO/CuO for CAP determination from commercial tablets and human urine samples further indicated the practical workability of the proposed electrode system.