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This study was aimed to determine the efficacy of 6-hydroxy melatonin and N-acetyl serotoninin protecting human retinal pigment epithelial cells from death brought about by oxidative-stress. The ARPE-19 cells (one of the retinal pigment epithelial cell lines) were used as the test cell culture. Following the application of 500 mM H 2 O 2 , ARPE-19 cell line culture was incubated for 20 h to induce oxidative stress damage. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assay was used to evaluate the oxidative injury to ARPE-19 cells caused by H 2 O 2 and the effectiveness of 6-hydroxy melatonin and N-acetyl serotonin application in preventing this damage. The results indicated that 6-hydroxy melatonin and N-acetyl serotonin exhibited a therapeutic effect on cells damaged by exposure to oxidative stress. It was concluded that these melatonin metabolites might be useful in treating many retinal conditions linked to the oxidative stress-induced damage. In addition, this study proposed a new idea for developing chemical approaches to the design and synthesis/semisynthesis of new drugs.