Reactive oxygen species (ROS), particularly hydrogen peroxide (H2O2 ), are critical mediators of oxidative stress, which can lead to cellular damage and contribute to various kidney diseases. Poria cocos, a traditional medicinal fungus, has demonstrated various health benefits, particularly in gastrointestinal and neurological health. This study investigates the potential of P. cocos extract (PCE) to reduce H2O2 -induced oxidative injury and promote cell proliferation in feline kidney epithelial cells. PCE treatment significantly improved cell viability in H2O2 -injured cells in a dose-dependent manner. PCE reduced intracellular ROS levels, including superoxide anions, hydroxyl radicals, and intracellular H2O2 , while enhancing the activities of antioxidant enzymes such as superoxide dismutase and catalase. Furthermore, PCE treatment promoted cell proliferation, as evidenced by increased Ki-67 expression, and enhanced the phosphorylation of ERK1/2 and AKT, which are key mediators of cell survival and proliferation. PCE effectively mitigates oxidative stress and promotes cell proliferation in kidney epithelial cells through the activation of the ERK1/2 and AKT pathways, suggesting its potential as a therapeutic agent for oxidative stress-related kidney diseases.