MicroRNAs (miRNAs) are a class of non-protein-coding RNA molecules with the ability to regulate gene expression at the posttranscriptional level, abundant in plants and animals, showing a high level of similarity due to their mechanism of biogenesis and action; this led to the discovery of cross-kingdom interactions mediated by exogenous miRNAs, which has been one of the most important scientific advances in recent years. Because plant-derived miRNAs after ingestion can be resistant to diverse conditions such as crossing the gastrointestinal tract in mammals, entering the body fluid and regulating the expression of endogenous mRNAs. Suggesting that food-derived plant miRNAs may control genes in humans through cross-kingdom regulation. More importantly, plant miRNAs may be a new class of molecules with utility in future epigenetic regulatory therapy applications in a wide range of diseases, demonstrating a new and highly specific strategy for the regulation of gene expression.