Indoles are aromatic heterocyclic organic compound and became the precursor to many pharmaceuticals. Indoles are found naturally in cruciferous plants and indole derivatives, indole-3-carbinole (I3C) and 3, 3’-diindolylmethane (DIM) can also be synthesized by a variety of methods. In vitro studies indicated that I3C and DIM inhibit cell proliferation, caused cell cycle arrest at G1 phase and induced apoptosis. The precise molecular mechanisms by which indole derivatives exert their tumor suppressive effects in human cancer cells are still unclear. It was reported that indoles alter estrogen metabolism. Microarray gene expression profiling and other studies indicated that indoles regulate many genes that are important for the control of cell cycle, cell proliferation, apoptosis, signal transduction, angiogenesis and cell invasion. In addition, it was found that indoles prevent tumor formation of breast and prostate cancer in animal models. Furthermore, these derivatives were evaluated in human clinical trials phase I and phase II as a potential chemopreventive agents against human breast, ovary, and vulvar intraepithelial neoplasia and colon cancers. Preliminary findings of these studies showed a significant clinical improvement. Interestingly, the use of indole derivatives was found to be safe without any indicated side effects. In conclusion, the results provide an evidence of the benefit of indole-derivatives in the prevention and treatment of hormone-dependent and hormone-independent human cancer. Further clinical trials are needed in order to approve the efficacy of indole derivatives in treatment of human cancer and to evaluate the indole use by the Food and Drug Administration (FDA).