Both plants and animals have adopted a common strategy of using ~18-25-nucleotide small non-coding RNAs (sncRNAs), known as microRNAs (miRNAs), to transmit DNA-based epigenetic information. miRNAs (i) shape the total transcriptional output of individual cells; (ii) regulate and fine-tune gene expression profiles of cell clusters, and (iii) modulate cell phenotype in response to environmental stimuli and stressors. These miRNAs, the smallest known carriers of gene-encoded post-transcriptional regulatory information, not only regulate cellular function in healthy cells but also act as important mediators in the development of plant and animal diseases. Plants possess their own specific miRNAs; at least 32 plant species have been found to carry infectious sncRNAs called viroids, whose mechanisms of generation and functions are strikingly similar to those of miRNAs. This review highlights recent remarkable and sometimes controversial findings in miRNA signaling in plants and animals. Special attention is given to the intriguing possibility that dietary miRNAs and/or sncRNAs can function as mobile epigenetic and/or evolutionary linkers between different species and contribute to both intra- and interkingdom signaling. Wherever possible, emphasis has been placed on the relevance of these miRNAs to the development of human neurodegenerative diseases, such as Alzheimer's disease. Based on the current available data, we suggest that such xeno-miRNAs may (i) contribute to the beneficial properties of medicinal plants, (ii) contribute to the negative properties of disease-causing or poisonous plants, and (iii) provide cross-species communication between kingdoms of living organisms involving multiple epigenetic and/or potentially pathogenic mechanisms associated with the onset and pathogenesis of various diseases.