Nanostructured biosensors with the aim of electroactive cancer-drug detection were investigated. The aim of this work is improvement of the sensitivity and limit of detection of two differently nanostructured biosensors to find out the best choice for quantifying the concentration of etoposide, as a widely used electroactive cancer drug, in its therapeutic range. To this purpose etoposide concentrations, ranging from zero to 60 μM, were sensed at multi-walled carbon nanotube and gold nanoparticle functionalized bioelectrodes using cyclic voltammetry. The optimum scan rate for voltammetric experiments was found out equal to 70 mV s-1 and 130 mV s-1 for multi-walled carbon nanotube and gold nanoparticle based electrodes, respectively. For nanostructuring the electrodes, the optimum nanomaterial mass were experimentally obtained for multi-walled carbon nanotube and gold nanoparticle based electrodes equal to 20 μ g (4314 mm of additional electroactive surface area) and 104 g (6471 mm of additional electroactive surface area), respectively. Bioelectrodes produced based on this optimized configurations showed sensitivity of 0.98 ± 0.41 μA μM-1 cm-2 and 1.43 ± 0.26 μA μM-1 cm-2, and limit of detection of 1.52 ± 0.89 μM and 1.29 ± 0.48 μM for multi-walled carbon nanotube and gold nanoparticles based electrodes. Comparing the limit of detection achieved in this work with the therapeutic range of etoposide verifies the possibility of using both nanostructured bioelectrodes for etoposide detection. However, gold nanoparticle based electrodes exhibit better electrochemical improvements in terms of both sensitivity and limit of detection.