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Pomegranate phenolics have been reported to exert skin beneficial effects but their mechanisms of action remain unclear. Herein, we investigated a standardized commercial pomegranate extract (PE; Pomella®) and its phenolics including punicalagin (PA), ellagic acid (EA), and urolithin A (UA) for their protective effects against hydrogen peroxide (H2O2)-induced oxidative stress and cytotoxicity in human keratinocyte HaCaT cells. PE, PA, and EA reduced the production of H2O2-induced ROS in HaCaT cells by 1.03-, 1.37-, and 2.67-fold, respectively. PE, PA, and UA increased the viability of H2O2-stimulated HaCaT cells by 89.9, 94.9, and 90.0%, respectively. PE, PA, and UA reduced apoptotic cell populations by 3.39, 7.11, and 8.26%, respectively. In addition, PE, PA and UA decreased H2O2-stimulated caspase-3 level by 2.31-, 2.06-, and 2.68-fold, respectively. The ameliorative effects of this PE and its phenolics against the H2O2-induced oxidative stress and cytotoxicity in keratinocytes support their utilization as natural cosmeceuticals for skin health.