Fabricating and designing a scaffold is a complex and highly challenging process in the current scenario. The present study deals with the design and fabrication of electrospun Santa Barbara Amorphous (SBA)-15-incorporated polyvinyl alcohol (PVA) with curcumin, which can be used as a biomimetic nanoscaffold for skin tissue engineering. Curcumin was selected due to its effective anti-microbial and anti-inflammatory properties. SBA-15 was selected for its characteristic drug-carrying potential. Fourier transform infrared spectroscopy and x-ray diffraction characterizations of the fabricated nanofiber demonstrated the interaction of PVA, SBA-15 and curcumin. The scanning electron microscopy results depicted that the nanofiber was highly interconnected with a porous structure mimicking the extracellular matrix. The nanofibrous scaffold showed a higher percentage of cell migration, proliferation, cytocompatibility and biocompatibility with absence of cytotoxicity which was evidenced from the results of MTT assay, cell adhesion and live/dead assay using HaCaT cells. The results of the anti-bacterial test depicted that the synthesized nanofiber forms a potent material for skin wound-healing therapeutics. The in vitro drug release study performed over a period of 80 h revealed a sustained release pattern of curcumin from the SBA-15-incorporated PVA nanofiber. Finally, the in vivo results confirmed that SBA-15-incorporated PVA nanofiber with curcumin showed efficient wound-healing activities.