This work investigates the incorporation of the Calendula officinalis (C. officinalis) extract in electrospun fiber scaffolds composed of poly (ε-caprolactone) (PCL), Zein and gum arabic (GA). Three methods of electrospinning were used: suspension electrospinning, in which C. officinalis extract was directly added in the PCL/Zein/GA solution, two-nozzle electrospinning, in which hybrid PCL/Zein/GA and PCL/C. officinalis nanofibrous layers were prepared by two syringes and multilayer electrospinning, in which layer-by-layer scaffold was fabricated of PCL/Zein/GA and PCL/C.officinalis nanofibrous mats. SEM micrographs of fabricated scaffolds depicted beadless nanofibers with interconnected pores. The PCL/Zein/GA/C.officinalis scaffolds possess good hydrophilicity with high porosity (about 80%) and also exhibited desirable mechanical properties and suitable degradability for skin tissue engineering. Multilayer produced scaffold showed more tensile strength than other C. officinalis-loaded PCL/Zein/GA scaffolds. In vitro C.officinalis release exposed gradual and sustained release behavior for fabricated scaffold by multilayer electrospinning. The results of MTT analysis and SEM images confirmed that PCL/Zein/GA/C.officinalis nanocomposite scaffold had favorable proliferation and adhesion against fibroblast cell as compared to PCL/Zein/GA scaffold for regenerating skin. The C. officinalis-loaded PCL/Zein/GA scaffold indicated better antibacterial properties and biocompatibility than PCL/Zein/GA scaffold. The results confirmed that C. officinalis-loaded PCL/Zein/GA nanocomposite scaffolds would be desirable biomaterial for skin regeneration.