Barley is a resilient crop with high nutritional value and adaptability, making it a promising candidate for phytoremediation and space agriculture. The study presents a comprehensive multi-omics analysis of the impact of ionising radiation (IR) on barley seedlings, intending to identify candidate pathways for creating radiation-resilient barley plants. We found that different IR treatments (gamma, electron, proton, neutron) increased the intensity of protein catabolism and led to the attenuation of translation. The impact of IRs on protein synthesis and degradation was accompanied by rearrangements in energy metabolism and reallocation of nitrogen, probably due to enhanced protein catabolism. At least partially, those changes seem to fuel secondary metabolites production, including riboflavin, various phytoalexins, phytosiderophores, ferulic and sinapic acids, kaempferol, quercetin, nictoflorin, gallate, and podophyllotoxin. Many of these compounds have antioxidant or radioprotective properties. To focus on possible targets for gene editing, we identified genes differentially regulated after all types of IR exposure and potential transcription factors regulating secondary metabolism, including AP2/ERF, WRKY, bHLH, bZIP, MYB, and NAC families.