A series of novel 5-(2-Carboxyethenyl) indole derivatives were designed and synthesized about 38-48% overall yields. Two of the seven newly synthesized compounds, compound 5 and 7, have not been reported before. Their structures were characterized on the basis of 1H, 13C NMR, and those compounds were tested for their anticancer activities against K562 and HT-29 cell lines. Results indicated that compounds 5, 6 and 7 containing 5-(2-Carboxyethenyl)indole derivatives demonstrated significant anticancer activity against HT-29 cell, their potency reached 4.67, 8.24 and 6.73 μM, respectively.