Nanofibrous electroactive composite scaffolds with sustained release properties based on polylactide (PLA) nanofibers and electroactive nanoparticles from polyurethane-urea copolymers were fabricated for tissue engineering applications. Electroactive polyurethane-urea copolymers were fabricated into nanoparticles which possessed sustained release kinetics for both hydrophobic and hydrophilic drugs. Composite scaffolds were obtained using an electrospray/electrospinning procedure with electroactive polyurethane-urea nanoparticles universally coated on PLA nanofibers. The morphology of nanoparticles, PLA fibers, and composite scaffolds was observed by SEM. The drug release profile of composite scaffolds was studied using ibuprofen and rutin as model drugs. The mechanism of the sustained release of the drugs was investigated. Rutin loaded composite material was used as an active scaffold for L929 fibroblast proliferation. Both random and aligned structures of electroactive composite PLA nanofibrous scaffolds were fabricated. The effect of surface chemistry and topographical cues on C2C12 cell proliferation and differentiation was studied on composite scaffolds, and it was found that electroactivity and aligned morphology of the composite nanofibers provide a synergetic effect for C2C12 myoblast proliferation and differentiation. These electroactive nanofibrous composite scaffolds with sustained release properties hold great potential for muscle and nerve regeneration.