The present review discusses about the contribution of microbiome that secrete antimicrobial peptides in association with residing microflora of the host imparting antimicrobial activity against invading pathogens. The relationship between antimicrobial peptides and microbiota of the intestine and their resultant effects on host health are highlighted. Defensins, cathelicidins, brevinins, ranalexin etc. can be harnessed as potential therapeutic targets for diseases like ileal Crohns disease, inflammatory bowel disease, colon cancer, etc. The bottom line is to make use of the antimicrobial peptides over the years to scientifically respond to infective agents in terms of therapeutic options in the treatment of animal diseases.