Electrospun poly(ϵ-caprolactone) (PCL) microfibers loaded with poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs) and curcumin with diameter of 3.9 ± 0.7 μm have been prepared and subsequently characterized using different spectroscopic techniques, scanning electron microscopy, and atomic force microscopy. PEDOT NPs, which are mainly located inside the PCL microfibers, exhibit a diameter of 99 ± 21 nm. PEDOT- A nd curcumin-containing PCL microfibers behave as extracellular cell matrices, facilitating cell spreading and enhancing cell proliferation because of their heterogeneity and roughness. The release of curcumin from the PCL microfibers by simple diffusion is very slow, external electric stimuli being required to boost and regulate the curcumin delivery process. PEDOT NPs behave as electroactuators upon application of well-defined potential pulses, increasing their diameter by about 17% and migrating from inside the PCL matrix to the surface of the microfibers. This electromechanical actuation mechanism affects the structure of the PCL matrix, promoting the release of curcumin that increases with the number of pulses. Overall, PCL fibers loaded with electroresponsive PEDOT NPs represent a promising and valuable drug delivery system that can be regulated by using pulsatile electrical stimulation.