Nowadays, aloe-vera (AV) is exploited extensively in nanofibrous structures for skin substitutes. However, the lack of electrospinnability and appropriate mechanical characteristics are the key limitations for this natural extract to be used in the form of nanofibrous mats. In this study, two commercially available biopolymers, gelatin (Gel) and poly(epsilon-caprolactone) (PCL), were chosen to improve these issues and double-nozzle electrospinning technique was used to fabricate hybrid scaffold from Gel/AV blend and PCL solutions. Response surface methodology was utilized to investigate the effect of electrospinning parameters (Gelatin concentration, Aloe-vera concentration and Gel/AV feed-rate) on the mechanical properties, morphology and hydrophilicity of nanofibers and the optimized scaffold was chosen for further studies. In order to verify the application of this scaffold in bioapplications, the chemical, thermal and biological features of scaffold were analyzed using FTIR, DSC, biodegradability, bactericidal, biocompatibility and drug-delivery. The results revealed that the presence of aloe-vera improved the antibacterial activity (> 99% and 85.63% against Gram-positive and Gram-negative bacteria, respectively), and led to adequate in-vitro biodegradation. Furthermore, it was found that incorporation of aloe-vera increased the cell viability without any toxicity.