Antibiotic-free approaches are more important than ever to deal with the rapidly growing problem of antibiotic resistance. The blue light 460nm (BL460nm) has been shown to effectively attenuate Staphylococcus aureus to chemical and physical agents through photolysis of the bacterial virulence factor Staphyloxanthin. However, the phototherapy using BL640nm has yet to be investigated in detail for its safety in eradicating Staphylococcus aureus in vitro and in vivo. In this study, we used a LED source producing a continuous wavelength of 460 nm along with hydrogen peroxide to treat S. aureus in culturing conditions and a wound abrasion mouse model. The results proved the safety of the combined therapy when it did not modify the bacterial virulence factors or the susceptibility to the widely used antibiotics. In addition, the experimental results on the mouse skin infection model also showed that the combined therapy is safe to apply to mouse skin and that it did not cause adverse skin irritation. Furthermore, the therapy can help Staphylococcus aureus-infected wounds heal with efficacy comparable to the topical antibiotic Fucidin. The above results suggest that the combination therapy of 460nm blue light and hydrogen peroxide can be safely used as an alternative to or adjunct to antibiotics in treating S. aureus-infected wounds.