In this study, we found that the highly expressed miRNAs appear in EPDELNs (Edible plant-derived exosome-like nanoparticles) have the potential to regulate human mRNA in a cross-kingdom manner. Target prediction and functional analysis revealed that highly expressed miRNAs were closely associated with inflammatory responses and cancer-related pathways. Therefore, we hypothesized that miRNAs in EPDELNs may be a crucial factor behind the regulatory function of EPDELNs. Overall design: We investigated miRNA expression profiles from 11 EPDELNs (Blueberry Coconut Ginger Grapefruit Hami melon Kiwifruit Pea Orange Pear Soybean Tomato) by using high-throughput sequencing technology.