The morbidity rate following a surgical procedure increasing rapidly in the cases associated with surgical site infections. Traditional sutures lack the ability to deliver drugs as the incorporation of the drug in their structure would hamper their mechanical properties. To prevent such infections, we developed an extracellular matrix mimicking electrospun nanofibrous yarns of poly-(D,L)-lactic acid and polyvinyl alcohol loaded with vancomycin and ferulic acid, prepared by uniaxial electrospinning technique. In-vitro characterization such as scanning electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction, tensile strength testing, degradation studies, and antimicrobial studies along with in-vivo evaluation done with help of incision wound healing rat model and simultaneous testing of microbial load in the incised tissue. The in-vitro studies indicated the nanofiber yarns have size range 200–300 nm with a tensile strength of 7.54 ± 0.58 MPa. The dual drug-loaded yarn showed sustained drug release over a period of 48 h. In-vitro water uptake and biodegradation data indicated optimum results suitable for suturing applications. Antimicrobial study showed excellent antimicrobial activity against both S. aureus and E. coli. Results obtained from in-vivo study suggested excellent wound healing potential of nanofiber yarns as compared with commercial silk sutures. The histopathological studies confirmed restoring ability of nanofiber yarn to the normal skin structure. Enzyme-linked immunosorbent assay (ELISA) study revealed the downregulation of inflammatory markers i.e. TNF-alpha and IL-6, making nanofibers sutures suitable for surgical wound healing applications. Overall, the present study may conclude that the developed dual drug-loaded nanofiber yarns have excellent potential in surgical wound healing applications.