UNLABELLED: Antimicrobial resistance has increased alarmingly in recent years, with the World Health Organization identifying multidrug-resistant as a particular threat to global public health due to its extensive resistance profile and associated high mortality rates. While various metal nanoparticles have been explored as antimicrobial agents, the specific advantages of biosynthesized copper nanoparticles against MDR remain inadequately consolidated in the literature. OBJECTIVE: This review uniquely evaluates the emerging evidence for biosynthesized copper nanoparticles as a sustainable, cost-effective, and potentially alternative to conventional antibiotics against multidrug-resistant strains. METHODS: We systematically analyzed current literature on green synthesis methods for copper and copper oxide nanoparticles, their characterization techniques, antimicrobial mechanisms, and efficacy against multidrug-resistant , focusing on identifying knowledge gaps and future research directions. RESULTS: Unlike other metal nanoparticles, biosynthesized copper nanoparticles demonstrate significant antibacterial activity against multidrug-resistant through multiple simultaneous mechanisms that bacteria try to develop resistance against. Their unique physicochemical properties enable enhanced bacterial elimination compared to conventional antibiotics and other metal nanoparticles, with minimal toxicity to mammalian cells at therapeutic concentrations. Our analysis further reveals the considerable potential of these nanoparticles to overcome existing biological barriers in infection sites that limit conventional therapies. CONCLUSION: This broad assessment of biosynthesized copper nanoparticles shows strong potential as a therapy against MDR and provides a foundation for future research to address antimicrobial resistance where current treatments fail.