Biofilm represents one of the crucial factors for the emergence of multi-drug resistance bacterial infections. The high mortality, morbidity and medical device-related infections are associated with biofilm formation, which requires primarily seek alternative treatment strategies. Recently, nanotechnology has emerged as a promising method for eradicating bacterial biofilm-related infection. The efficacy of nanoparticles (NPs) against bacterial infections interest great attention, and the researches on the subject are rapidly increasing. However, the majority of studies continue to focus on the antimicrobial effects of NPs in vitro, while only a few achieved in vivo and very few registered as clinical trials. The present review aimed to organize the scattered available information regarding NPs approach to eradicate bacterial biofilm-related infections. The current review highlighted the advantages and disadvantages associated with this approach, in addition to the challenges that prevent reaching the clinical applications. It was appeared that the production of NPs either as antimicrobials or as drug carriers requires further investigations to overcome the obstacles associated with their kinetic and biocompatibility.