Plant-derived edible nanoparticles (PDNPs) and microRNAs (miRNAs) represent a new emerging tool for boosting human health and nutrition. Here, the properties and sources of PDNPs along with their application, and further the biology and importance of miRNAs in plants and humans, will be discussed. PDNPs are nanovesicles obtained from edible plants with the capability of encapsulating bioactive compounds that include miRNAs. They are biocompatible, stable, and have the feature of targeted delivery. miRNAs participate in the regulation of gene expression and act as mediators of stress responses in plants under various environmental stressors. The interactions between PDNPs and miRNA facilitate cross-kingdom communication and have prospects for new therapeutic strategies. Key applications of PDNPs and miRNAs are antioxidant and anti-inflammatory effects, gut health maintenance, tissue regeneration, and cancer therapy. Despite these challenges, the potential for PDNPs and miRNAs in furthering personalized nutrition and medicine is significant. There is a lot more interdisciplinary research needed to bring this potential fully into human health benefits.