Phytochemical investigation of aerial parts of C. colocynthis resulted in isolation of two new sesquiterpineMS-6 (Germacr-3-ol-8-en-6,12-oxy-15-oic acid) and MS-2 (5,6-[4,butyl-1,3-dioxino]-7-ene-oxecine) along with several known compounds. The two compounds have shown potent anti-fungal activity evaluated by using of Cup-Plate agar diffusion method. These compounds may provide a chemical moiety for more potent analogues.