Calotropis procerais traditionally used for treating many diseases including ulcers and tumors. It was thus deemed of interest to investigate and compare the antiulcer and cytotoxic activities ofC. proceraleaf, flower, and fruit extracts in an attempt to verify its traditional uses. Phytochemical studies on the fruits, flowers, and leaves ofC. procera,collected from the desert of Saudi Arabia, led to the isolation of one new lignan 7′-methoxy-3′-O-demethyl-tanegool-9-O-β-D-glucopyranoside and five known compounds from the flowers, four compounds from leaves, and a flavonoid glycoside and a lignan glycoside from the fruits. The structures of compounds were determined by spectroscopic techniques. Ethanol extracts of the three parts ofC. procerawere evaluated for their antiulcer activity and we found that the leaf extract possessed a powerful antiulcer activity which could be considered as a promising drug candidate. All the extracts and the isolated compounds were evaluated for their cytotoxic activity against MCF-7, HCT-116, HepG-2, and A-549 human cancer cell lines. Compound2was highly active on all the cell lines, whereas compounds5and11were more selective on colon and liver cell lines. Compound10demonstrated a significant activity on liver and lung cancer cell lines.