As a central component of the hydrogen peroxide detoxifying system in plant cells, ascorbate peroxidases (APX) play an essential role in the control of intracellular reactive oxygen species (ROS) levels. To characterise the function of cytosolic APX isoforms (OsAPX1 and OsAPX2) in the mechanisms of plant defence, OsAPX1/2 knockdown rice plants were previously obtained. OsAPX1/2 knockdown plants (APx1/2s) exhibited a normal phenotype and development, even though they showed a global reduction of APX activity and increased hydrogen peroxide accumulation. To understand how rice plants compensate for the deficiency of cytosolic APX, expression and proteomic analyses were performed to characterise the global expression pattern of the APx1/2s mutant line compared with non-transformed plants. Our results strongly suggest that deficiencies in cytosolic APX isoforms markedly alter expression of genes associated with several key metabolic pathways, especially of genes involved in photosynthesis and antioxidant defence. These metabolic changes are compensatory because central physiological processes such as photosynthesis and growth were similar to non-transformed rice plants. Our analyses showed modulation of groups of genes and proteins related to specific metabolic pathways. Among the differentially expressed genes, the largest number corresponded to those with catalytic activity. Genes related to oxidative stress, carbohydrate metabolism, photosynthesis and transcription factor-encoding genes were also modulated. These results represent an important step toward understanding of the role played by cytosolic APX isoforms and hydrogen peroxide in the regulation of metabolism by redox modulation in monocots.