C. monacantha has been previously investigated for its phytochemical compounds where 13 triterpenoidal saponins, 6 flavonoid derivatives and 4 Gallotannins have been reported. The aerial part of C. monacantha is known in folk medicine, especially in desert and rural areas of North Africa and Middle East where this plant is growing, for the treatment of jaundice and other liver diseases, it has also purgative effect and increase the milk supply for camels. The purpose of present study includes biological investigation of different C. monacantha extracts. The total alcoholic extract of C. monacantha was fractionated into four fractions; ether, ethyl acetate, saponins and acetone fractions. Different C. monacantha fractions have been investigated for the first time in the present study regarding their hepatoprotective, antidiabetic, anti-inflammatory, antioxidant, antimicrobial and cytotoxic activities. The most active fraction was ethyl acetate fraction while the saponins fraction showed the lowest effect in all biological screening tests. Further investigation of the ethyl acetate fraction is recommended to explain and identify the correlation between the phytochemical constituents of ethyl acetate fraction of C. monacantha and the biological activities.