In the last decade, the use of natural antimicrobial agents such as polyphenolic extracts (PE) for postharvest applications have been gaining attention. However, this technology presents a major challenge in the coming years. The possibilities of production on a commercial scale, practical applications and their technical and economic feasibility compared to conventional agrochemicals must be clearly demonstrated. The objective of this review is to demonstrate the success and challenges of the investigation of PE extracts from Mexican crops as antimicrobial agents, against phytopathogens and food-borne microorganisms in postharvest processes. Mainly, it focuses on extracts obtained from crops such as: Habanero chili pepper (Capsicum chinense Jack), Jackfruit (Artocarpus heterophyllus Lam), Broccoli (Brassica oleracea var. italica), Allspice (Pimienta dioica). Additionally, the interaction of the main phytochemicals presents (i.e., capsaicin, sulforaphane, eugenol) in the extracts obtained was analyzed using quantic chemistry. In-depth knowledge of the molecular mechanisms of these substances against pathogens under in vitro and mainly in vivo conditions, and knowledge of plant systems will allow better results to be obtained. The toxicity evaluation of extracts and their effect on organoleptic properties of the fruit must be determined. Besides, the use of coating and encapsulation techniques as emerging methods for improving the effectiveness of extracts must be considered also. The integral approach for improving the efficiency of treatments and cost effectiveness control programs of preharvest, harvest, and post-harvest processes must be developed. Finally, the successful implementation on commercialization of these technologies will depend of cost-benefit of processes. The infrastructure, raw material availability, local needs and technical facilities, among other factors are indispensable conditions for this. Furthermore, the cost and energy sustainability, applying strategies related with circular economy will enhance the efficiency of the plant residues utilization and to develop technological and marketing approaches.