Food is the essential need of human life and has nutrients that support growth and health. Gastrointestinal tract microbiota involves valuable microorganisms that develop therapeutic effects and are characterized as probiotics. The investigations on appropriate probiotic strains have led to the characterization of specific metabolic byproducts of probiotics named postbiotics. The probiotics must maintain their survival against inappropriate lethal conditions of the processing, storage, distribution, preparation, and digestion system so that they can exhibit their most health effects. Conversely, probiotic metabolites (postbiotics) have successfully overcome these unfavorable conditions and may be an appropriate alternative to probiotics. Due to their specific chemical structure, safe profile, long shelf-life, and the fact that they contain various signaling molecules, postbiotics may have anti-inflammatory, immunomodulatory, antihypertensive properties, inhibiting abnormal cell proliferation and antioxidative activities. Consequently, present scientific literature approves that postbiotics can mimic the fundamental and clinical role of probiotics, and due to their unique characteristics, they can be applied in an oral delivery system (pharmaceutical/functional foods), as a preharvest food safety hurdle, to promote the shelf-life of food products and develop novel functional foods or/and for developing health benefits, and therapeutic aims. This review addresses the latest postbiotic applications with regard to pharmaceutical formulations and commercial food-based products. Potential postbiotic applications in the promotion of host health status, prevention of disease, and complementary treatment are also reviewed.