Microbial resistance to conventional therapeutics has become a significant threat to human society. Biofilms serve as the major virulence factor for the microorganisms by resisting the antibiotics and host innate immune system. Antimicrobial peptides (AMPs) have emerged as a potential alternative to conventional therapeutics due to their exceptional anti-biofilm and broad-spectrum antimicrobial property. Researchers have applied bioinformatics, genetic engineering, tissue culture, and drug delivery approaches to enhance the production and therapeutic efficacy of antimicrobial peptides. This review comprehensively describes the various aspects of AMPs with particular focus on their anti-biofilm potential. Other detailed information highlighted in this review includes different classes of AMPs, their mode of action, and anti-biofilm activity both alone and in synergy with other AMPs or conventional antibiotics. Further, challenges and opportunities of AMPs based drug delivery systems such as nano-formulations, polymeric micelles, and vesicles are also summarized.