Among Arabidopsis Nudix hydrolases (AtNUDX1~27), AtNUDX6 and AtNUDX7 having ADP-ribose/NADH pyrophosphohydrolase activities have been found to contribute to keeping the energy and redox homeostasis, and/or modulating defense responses against biotic and abiotic stress. Interestingly, AtNUDX6 had an opposite effect to AtNUDX7 on the regulation of immune responses. A comparison of the activities of ADP-ribose/NADH pyrophosphohydrolase among wild-type, knockout (KO)-AtNUDX6, and KO-AtNUDX7 plants revealed AtNUDX7 to contribute more than AtNUDX6 to the total pyrophosphohydrolase activity toward both ADP-ribose and NADH under normal conditions and oxidative stress, while AtNUDX6 accounted for the majority of total NADH pyrophosphohydrolase activity under salicylic acid treatment. These results support the idea that the metabolism of ADP-ribose and/or NADH needs to be finely tuned for accurate regulation of cellular responses to biotic and abiotic stress.