Traditional means of contaminant management that rely on chemical additives and high-temperature processing have raised concerns about long-term safety and environmental issues in the modern food supply chain. Therefore, sustainable, safe, and innovative strategies are urgently needed. Plant-derived substances are known for their biological activity and antifouling potential as natural alternatives for contamination control. This review examines the sources of various contaminants, the categories of plant-derived substances, the action mechanisms, and their feasibility in the food supply chain. The smart use of plant-derived substances to improve microbial, chemical, and metal contamination in the food blockchain is not only a profound fusion of nature and technology, but also a mutual combination of ecological preservation and food safety. However, the realization of its commercialization is subject to multiple sanctions, but as the thorny issues are gradually resolved, the consolidation and market for the new strategies will thrive.