Staphylococcus aureus is a leading cause of nosocomial and community-acquired infections. The formation of biofilm by this pathogen renders it resilient to antimicrobial agents, which complicates the treatment of such infections. S. aureus can form biofilms with other pathogens and cause polymicrobial infections recalcitrant to antimicrobial agents. Therefore, anti-biofilm agents against which this bacterium cannot develop resistance are a highly desirable treatment strategy. Nanoparticles and some non-antimicrobial drugs proposed for various clinical purposes have proven to be excellent antibacterial and anti-biofilm agents to control S. aureus biofilm infections. A variety of chemically distinct compounds capable of acting as anti-biofilm agents against S. aureus have been extracted from microbial sources. This review explains the characteristics of S. aureus biofilms, emphasizing the therapeutic potential of nanoparticles, repurposed drugs, and anti-biofilm agents from microbial sources to combat S. aureus biofilm infections.