The electrospun core-shell nanofiber has great many advantages such as different types of solvents that can be used for changing flexibility, mechanical properties, or surface chemistry of fiber. Hydrophobic Poly(lactic) acid (PLA) and hydrophilic gelatin (Gel) were electrospun by various preparation conditions to design perfect bicomponent PLA:Gel nanofiber in a core-shell structure. Solvent types, the concentration of polymeric components, flow rate, and voltage of the electrospinning process were changed to optimization of nanofiber. According to the SEM images, the best nanofiber structure without beads was obtained at 0.4 ml/h flow rate of PLA solution and 1.2 ml/h flow rate of Gel solution at 45:55 (w:w %) weight ratio of PLA:Gel in trifluoroethanol solvent with a 10 kV voltage at 10 cm distance to the collector. From the TEM images, the existence of the core-shell structure had been proved which all prepared nanofibers with 2,2,2-Trifluoroethanol solvent. Furthermore, contact angle measurements showed a change in wettability when the Gel amount was increased. Therefore, the mildest synthesis conditions were determined for bicomponent PLA:Gel core-shell nanofibers as a potential wound dressing and dual drug carrier materials.