Vancomycin Staphylococcus aureus (VRSA) is a strain of S. aureus that is considered the main cause of bacterial skin and soft tissue infections. It has acquired resistance to vancomycin and represents a therapeutic challenge. The current study aimed to compare the possible therapeutic effects of VRSA bacteriocin (VRSAcin) on the treatment of skin infection in mice with those of an antibiotic (linezolid). The results showed that of the fifty swabs obtained from human skin wounds. One isolate was selected for VRSAcin extraction depending on its antibiotic resistance using an antibiotic susceptibility test.An agar well diffusion test was used to determine bacteriocin’s antibacterial activity, as well as its a minimum inhibitory concentration, minimum bactericidal concentration, and antibiofilm efficiency against gram-positive and gram-negative bacteria that were resistant to many medicines. The freshly developed antibacterial substance VRSAcin shows promise. Bacteriocin from VRSA was extracted and studied the optimal conditions for the Production following Purification of bacteriocin by ammonium sulfate precipitation followed by cation-exchange chromatography. The molecular weight of bacteriocin about (29 kDa) were determined by Sodium Dodecyl Sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The typical conditions for the production of VRSAcin include a pH of 7 and a temperature of 37 ◦C for 48 h. In mice, VRSA-contaminated wounds revealed severe tissue distraction and inflammation that extended to the hypodermis, while VRSA-treated skin showed mild changes and localized lesions to the epidermis and upper dermis. The skin of linezolid ointment-treated mice showed moderate to severe changes. In conclusion, VRSA strain infections in human burned skin were more common than expected. In vivo studies in mice indicated that wounded skin infected with VRSA can be treated with VRSAcin as an antibacterial agent that promotes healing processes with obvious superiority to linezolid ointment. As a result, the VRSA develops bacteriocins that are appropriate for regulating AMR, Gram-positive and Gram-negative bacteria, and may be useful in wound dressings.