Overproduced reactive oxygen species (ROS) are closely related to various health problems including inflammation, infection, and cancer. The abnormally high ROS level can cause serious oxidative damage to biomolecules, cells, and, tissues. A series of nano- or micro-sized particles has been developed to reduce the oxidative stress level by delivering antioxidant drugs. However, most systems are often plagued by the slow molecular discharge driven by diffusion. In this work, we demonstrate an active antioxidizing polymeric particles that can increase the internal pressure in response to the abnormal ROS level and thus actively discharge antioxidants to protect cells and tissues from the oxidative damage. The on-demand pressurized particles particle was assembled by simultaneously loading water-dispersible manganese oxide (MnO2) nanosheets and green tea-derived antioxidant into poly(lactic-co-glycolic acid) (PLGA) spherical shell. In the presence of H2O2, one of the ROS, MnO2 nanosheets in the PLGA particle generated oxygen gas by decomposing H2O2 and increased the internal pressure. Accordingly, the active antioxidizing particle system could release a larger fraction of antioxidants and effectively protect endothelial cells and brain tissues from H2O2-induced oxidative damage. We believe that this H2O2-responsive, self-pressurizing particle system would be useful to deliver a wide array of molecular cargos in response to the oxidation level.