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Food-borne illnesses are a significant concern for consumers, the food industry, and food safety authorities. Natural preservatives are very crucial for enhancing food safety and shelf life. Therefore, this review aimed to assess the literature regarding the potential of natural preservatives to enhance food safety and extend the shelf life of food products. The review paper indicated that natural antimicrobial agents that inhibit bacterial and fungal growth for better quality and shelf life have been of considerable interest in recent years. Natural antimicrobials are mainly extracted and isolated as secondary metabolites of plants, animals, and microorganisms. Plants, especially herbs and spices, are given more attention as a source of natural antimicrobials. Microorganisms used in food fermentation also produce different antimicrobial metabolites, including organic acids, hydrogen peroxide, and diacetyl, in addition to bacteriocins. Products of animal origin, such as tissues and milk, contain different antimicrobial agents. Natural antimicrobials are primarily extracted and purified before utilization for food product development. The extraction condition and purification of natural preservatives may change their structure and affect their functionality. Selecting the best extraction method coupled with minimal processing such as direct mechanical extraction seems to preserve active ingredients. The activity of natural antimicrobials could also be influenced by the source, time of harvesting, and stage of development. The effectiveness of natural antimicrobial compounds in food applications is affected by different factors, including food composition, processing method, and storage conditions. Natural antimicrobials are safe because they can limit microbial resistance and meet consumers' demands for healthier foods.