Sesame (Sesamum indicum L.) seeds contain abundant oil and antioxidative lignans related to the seed quality. To evaluate the potential effects of drought stress on the chemical composition of sesame seeds, eighteen cultivars were imposed water-deficit condition by withholding irrigation during 15 days at podding and maturing stage, compared with well-watered plants as control in seed yield and chemical composition. Drought treatments showed great decrease of seed yield with not affecting seed weight. The contents of sesamin and sesamolin decreased while lignan glycosides inversely increased in response to drought stress. Oil content was not significantly changed by drought treatment in spite of its slight decrease. In case of fatty acid composition, there were significant differences in increase of oleic acid while inverse decrease of linoleic acid under drought stress condition. These results demonstrate that the chemical composition of sesame seed may be modified with drought stress. In particular, the increase of sesaminol glucosides with strong antioxidative activity was observed.