Electrospun polylactide nanofibers loaded with different antioxidants (i.e. vitamin B6 in pyridoxine and pyridoxal form, p-coumaric acid and caffeic acid) are prepared from N,N-dimethylformamide/dimethylsulfoxide solutions. Morphology, structure and crystallinity of the nanofibers are evaluated by transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray diffraction and differential scanning calorimetry (DSC) techniques. Fibers are highly amorphous but able to crystallize easily due to the high molecular orientation induced by the electrospinning process. The drug molecules are incorporated into the polymeric matrix or formed isolated crystals. A fast release of loaded drug occurs within the first 8 h in hydrophobic medium; but, a slow and sustained release during several days occurs in a hydrophilic medium. Cell attachment on the loaded scaffolds was unaffected by the incorporation of the antioxidants. In contrast, cell proliferation increases with high antioxidative activity against free radicals responsible for cell damage. These new electrospun scaffolds provide high protection of cells against oxidative stress and resulting in innovative 3D fibrous platforms for tissue growth and proliferation.