Antibiotic resistance remains a pressing global health concern, necessitating the development of sustainable and innovative antimicrobial strategies. Plant-based nanomaterials, particularly those synthesized from agricultural byproducts, such as mango seeds, tomato skins, and orange peels, have emerged as promising candidates due to their potent antimicrobial activity and reduced likelihood of resistance development. These nanomaterials exert their effects through diverse mechanisms, including the generation of reactive oxygen species, the disruption of microbial membranes, and interference with critical cellular functions, such as DNA replication. Beyond their antimicrobial properties, recent studies have demonstrated their ability to modulate gut microbiota composition-promoting beneficial genera such as, and , while inhibiting pathogenic species like spp. This dual functionality positions them as attractive agents for prebiotic interventions and targeted dietary strategies. The convergence of plant-derived nanotechnology and personalized nutrition, guided by individual microbiota profiles, offers a novel paradigm for enhancing host health and preventing infection-related disorders. This review provides a comprehensive overview of the sustainable production of nanomaterials from agricultural and food industry waste, their antimicrobial and prebiotic applications, and their potential in regulating gut microbiota. Furthermore, we discuss emerging nanoenabled strategies to combat infectious diseases and highlight future directions for mechanistic studies, safety assessments, and clinical translation in pharmaceutical, nutraceutical, and functional food contexts.