Staphylococcus aureus is a fatal Gram-positive pathogen threatening numerous cases of hospital-admitted patients worldwide. The emerging resistance of the pathogen to several antimicrobial agents has pressurized research to propose new strategies for combating antimicrobial resistance. Novel strategies include targeting the virulence factors of S. aureus. One of the most prominent virulence factors of S. aureus is its eponymous antioxidant pigment staphyloxanthin (STX), which is an auspicious target for anti-virulence therapy. This review provides an updated outline on STX and multiple strategies to attenuate this virulence factor. The approaches discussed in this article focus on bioprospective and chemically synthesized inhibitors of STX, inter-species communication and genetic manipulation. Various inhibitor molecules were found to exhibit appreciable inhibitory effect against STX and hence would be able to serve as potential anti-virulence agents for clinical use.