Emerging issues of Antibiotic drug resistance have increased the mortality cases all around the world. To deal with the situation natural antimicrobial peptide (AMP) replaces the classic antibiotics. Antimicrobial peptides are short, natural peptides that are active against most bacteria’s, viruses, and fungi etc., The AMP acts as a potent therapeutic agent and finds a new way in the field of drug discovery and pharmaceuticals. One such antimicrobial peptide is gramicidin (gramicidin D and gramicidin S) has high potential of almost 100% killing mechanisms against most of the gram-positive and few gram-negative bacteria’s and fungi which can be used as an alternative antibiotic in the near future. There are reviews focusing only on individual types of gramicidin or particular about their function. Hence, this review focus on providing an overview of antimicrobial peptide gramicidin and its types, structures, its interaction with the membranes/lipid bilayers, functions, stability, and uses. This review also focuses on the challenges to enhance the gramicidin peptide for further use as an efficient effective therapeutic peptide in the pharmaceutical industries. © 2019, Springer Nature B.V.