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Microorganism contamination at various stages of food chain is one of the major causes for food spoilage that ultimately leads to food waste, increasing food insecurity issues and substantial economic losses. Various synthetic chemical preservatives are being used to control microbial food spoilage and to extend product shelf life. Researchers and consumers are discouraging the use of synthetic preservatives due to their negative health impacts. Naturally occurring antimicrobials have gained attention among researchers and food manufacturer due to their safety and nontoxic status. Natural preservatives are easy to obtain from plants, animals and microbes. These naturally occurring antimicrobial agents can be isolated from indigenous sources using various advanced techniques. Natural preservatives such as nisin, essential oils, and natamycin have effective potential against spoilage and pathogenic microorganisms. The regulations regarding the use of these naturally occurring preservatives are not well defined in some developing countries. This chapter focuses on source and their potential role, antimicrobial mechanism in food preservation, and current knowledge on the subject.