As high telomerase activity is detected in most cancer cells, telomerase represents a promising cancer therapeutic target. We investigated the inhibitory effect of sulfoquinovosyldiacylglycerol (SQDG), distributed in plants and seaweeds, on human telomerase in a cell-free system. SQDG inhibited telomerase activity dose-dependently with 50% inhibition at 22 microM, whereas monogalactosyldiacylglycerol and digalactosyldiacylglycerol did not, even at concentrations of 100 microM. Moreover, we confirmed that eicosapentaenoic acid, one of the fatty acid components of SQDG, is a potent telomerase inhibitor with 50% inhibition at 19 microM. We speculate that the structure of the sulfate group and fatty acid of SQDG is important for the potent telomerase-inhibitory effect. Our findings suggest that SQDG has potential use as a therapeutic dietary compound for telomerase inhibition.