In recent years, the widespread use of antimicrobial agents has led to the emergence of multidrug-resistant Staphylococcus aureus, which pose a serious challenge to clinical therapy. The use of antimicrobial agents increases bacterial resistance, so it is necessary to find alternative therapy. In this paper, the potential alternative therapy to antimicrobial agents in recent years was reviewed, which including anti-biofilm activity agents (biosurfactant, magnetic nanoparticle, bacteriophage lysin, bacteriocin, histones, lysophosphatidylcholine, essential oil), antimicrobial photodynamic therapy, and immunomodulator, so as to help to reduce bacterial resistance.