Fresh leaf skin aqueous and methanolic extracts as well as shade-dried leaf skin methanolic extracts prepared separately from the leaves of Aloe vera and aloe emodin (AE) were assayed on human gastric (AGS), colon (HT-29, HCT116) and hepatocellular (HEPG2) cancer cell lines relative to human umbilical vein endothelial cells (HUVEC). AE, 5-fluorouracil (5-FU) and imatinib (IM) were tested as positive controls. Among the four extracts studied, A. vera gel extract (AVG) had the highest cytotoxic effect on cancer cells, with the highest effect on HCT116 cells, while no cytotoxic effect on HUVEC cells was detected. AE has also selective cytotoxic and apoptotic effects on the cancer cells and was ineffective on normal cells. AVG treatment in HCT116 cells induced the apoptosis by the activation of caspase-9 and caspase-3. According to our results, AVG and AE could be proposed as promising cytotoxic drugs from natural origin.