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Abstract Curcuma zedoaria is a traditional medicine used for various purposes in human life. The organic solvent extracts of this plant also exhibit antioxidant, antibacterial, anti-inflammatory, anti- cancer, anti-necrosis, and hepatoprotective properties. However, the prospect of employing this plant extract for skin whitening, particularly its molecular mechanism, has not been reported yet. Therefore, in this study, the total polyphenolic content, antioxidant activity, cytotoxicity, tyrosinase inhibitory, melanin inhibitory, and target gene expression using the ethyl acetate fraction of ethanolic extract from Curcuma zedoaria , were all examined. The TPC result of the sample was 42.18±2.25 mg GAE/g extract with impressive antioxidant activity. Half maximal inhibitory concentration value of 2,2-Diphenyl-1-picrylhydrazyl radical scavenging assay and Ferric reducing antioxidant power FRAP value at a concentration of 2.5 µg/mL were 49.06±0.29 µg/mL and 116±50 μM Fe2+/L, respectively. The extract had no cytotoxicity at 25 µg/mL, inhibited melanin production for 74.02±3.05% and tyrosinase for 137.45±1.38%. In particular, the extract demonstrated the ability to block the expression levels of four melanogenesis-related genes. Moreover, GCMS analysis results also detected 28 different compounds, with two new compounds accounting for a high proportion. These results suggested that C. zedoaria has a significant potential for application in skin-pigmentation treatment cosmetics. life antibacterial antiinflammatory, antiinflammatory anti inflammatory, inflammatory anti-inflammatory cancer antinecrosis, antinecrosis necrosis, necrosis anti-necrosis properties However whitening mechanism yet Therefore study content activity examined 4218225 42 18 2 42.18±2.2 GAEg GAE g 2,2Diphenyl1picrylhydrazyl 22Diphenyl1picrylhydrazyl Diphenylpicrylhydrazyl 2,2 Diphenyl 1 picrylhydrazyl 5 2. µgmL µg mL 4906029 49 06 0 29 49.06±0.2 11650 116 50 116±5 Fe2L FeL Fe2 L Fe Fe2+/L respectively 7402305 74 02 3 05 74.02±3.05 13745138 137 45 38 137.45±1.38% particular melanogenesisrelated melanogenesis related genes Moreover proportion C skinpigmentation pigmentation cosmetics 421822 4 42.18±2. 2Diphenyl1picrylhydrazyl 22 2, 490602 49.06±0. 1165 11 116± 740230 7 74.02±3.0 1374513 13 137.45±1.38 42182 42.18±2 49060 49.06±0 74023 74.02±3. 137451 137.45±1.3 4218 42.18± 4906 49.06± 7402 74.02±3 13745 137.45±1. 421 42.18 490 49.06 740 74.02± 1374 137.45±1 42.1 49.0 74.02 137.45± 42. 49. 74.0 137.45 74. 137.4 137.