Plants, being sessile, are prone to genotoxin-induced macromolecule damage. Among the inevitable damaging agents are reactive carbonyls that induce glycation of DNA, RNA and proteins to result in the build-up of advanced glycated end-products. However, it is unclear how plants repair glycated macromolecules. DJ-1/PARK7 members are a highly conserved family of moonlighting proteins having double domains in higher plants and single domains in other phyla. Here we show that Arabidopsis DJ-1D offers robust tolerance to endogenous and exogenous stresses through its ability to repair glycated DNA, RNA and proteins. DJ-1D also reduced the formation of reactive carbonyls through its efficient methylglyoxalase activity. Strikingly, full-length double domain-containing DJ-1D suppressed the formation of advanced glycated end-products in yeast and plants. DJ-1D also efficiently repaired glycated nucleic acids and nucleotides in vitro and mitochondrial DNA in vivo under stress, indicating the existence of a new DNA repair pathway in plants. We propose that multi-stress responding plant DJ-1 members, often present in multiple copies among plants, probably contributed to the adaptation to a variety of endogenous and exogenous stresses.