Plant phenolics as secondary metabolites are key to a plant's defense response against biotic and abiotic stresses. These phytochemicals are also increasingly relevant to food preservation and human health in terms of chronic disease management. Phenolic compounds from different food crops with different chemical structures and biological functions have the potential to act as natural antioxidants. Plant-based human foods are rich with these phenolic phytochemicals and can be used effectively for food preservation and bioactive enrichments through metabolic stimulation of key pathways. Phenolic metabolites protect against microbial degradation of plant-based foods during postharvest storage. Phenolics not only provide biotic protection but also help to counter biochemical and physical food deteriorations and to enhance shelf life and nutritional quality. This review summarizes the role of metabolically stimulated plant phenolics in food preservation and their impact on the prevention of oxidative stress-induced human diseases.