In this study, the calyx of Diospyros kaki was evaluated for antioxidative activity using HepG2 cells treated with alcohol-induced oxidative stress and quantitatively analyzed for phenolic acids and flavonoid concentration by LC-MS/MS. The extract of the calyx of Diospyros kaki showed no significant toxicity to HepG2 cells till a concentration of 10 μg/mL was reached and displayed increased cell viability compared to the 3% ethanol-treated group. The extract inhibited the production of reactive oxygen species at all concentrations. Besides, the extract inhibited malondialdehyde production at all concentrations and the inhibitory effect was higher than the positive control (esculetin 100 μM). Also, the extract increased the concentration of glutathione. The major phenolic acids and flavonoid in the extract were vanillic acid (729.01±42.48 μg/g) and catechin (1,894.89±105.10 μg/g), respectively. This study shows that the calyx of Diospyros kaki can be used as a functional material that exhibits antioxidative and hepatoprotective effects.