The moon reflects the sun light at very low intensity (less than 0.0008% of sunlight), yet, it has a broad effect on reproduction, communication, foraging and predation in invertebrates, birds, reptiles, and mammals. Rhythmic exposure to moonlight is believed to affect the life cycle of plants, from seed germination to fruit ripening and dispersal. A basic principle in traditional lunar farming is that above-ground crops should be planted on the days between new moon and full moon, while below-ground crops should be planted between full moon and the next new moon; yet these agricultural practices lack solid scientific background. We investigated the effect of exposure of tobacco plants to full moonlight (FML) on genome organization and protein and metabolite profiles. Results showed that exposure to FML as well as to growth room light for 5h induced a significant increase in nuclear size accompanied by reduction in CG methylation of centromeric RS-3-19 repeats compared to dark, indicating that induction of genome reorganization is independent on light intensity. Many stress-responsive metabolites such as proline, serine, glutamic acid, and raffinose were up-regulated in FML-exposed plants. Proteomic analysis showed that the photoreceptors Phytochrome B, phototropin, as well as stress-responsive proteins such as heat shock proteins, chaperonins and peroxidases were up-regulated in FML plants when compared to dark. Our data suggest that FML is perceived as a stress signal accompanied by modification of genome organization, which might lead to changes in gene expression pattern and metabolic activity of the cells.