Hydrolysis and aminolysis are two main commonly used chemical methods for surface modification of hydrophobic tissue engineering scaffolds. The type of chemical reagents along with the concentration and treatment time are main factors that determine the effects of these methods on biomaterials. In the present study, electrospun poly (ℇ-caprolactone) (PCL) nanofibers were modified through hydrolysis and aminolysis. The applied chemical solutions for hydrolysis and aminolysis were NaOH (0.5–2 M) and hexamethylenediamine/isopropanol (HMD/IPA, 0.5–2 M) correspondingly. Three distinct incubation time points were predetermined for the hydrolysis and aminolysis treatments. According to the scanning electron microscopy results, morphological changes emerged only in the higher concentrations of hydrolysis solution (1 M and 2 M) and prolonged treatment duration (6 and 12 h). In contrast, aminolysis treatments induced slight changes in the morphological features of the electrospun PCL nanofibers. Even though surface hydrophilicity of PCL nanofibers was noticeably improved through the both methods, the resultant influence of hydrolysis was comparatively more considerable. As a general trend, both hydrolysis and aminolysis resulted in a moderate decline in the mechanical performance of PCL samples. Energy dispersive spectroscopy analysis indicated elemental changes after the hydrolysis and aminolysis treatments. However, X-ray diffraction, thermogravimetric analysis, and infrared spectroscopy results did not show noticeable alterations subsequent to the treatments. The fibroblast cells were well spread and exhibited a spindle-like shape on the both treated groups. Furthermore, according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the surface treatment procedures ameliorated proliferative properties of PCL nanofibers. These findings represented that the modified PCL nanofibrous samples by hydrolysis and aminolysis treatments can be considered as the potentially favorable candidates for tissue engineering applications.