The potential antischistosomal activity of Conus muscle extract on the adult worms of Schistosoma mansoni was studied In vitro. Live specimens of five common species of cone snails were collected from several locations on the Egyptian Red Sea coast. The muscles of these snails had been collected after crushing their shells to prepare the muscle extracts. The adult worms of S. mansoni were isolated from the blood circulation by perfusion technique using phosphate buffer. After 1- 4 days of exposure to cone snails muscle extracts at varying doses, the worm's motility and mortality rates were examined. The results showed that muscle extracts of 3 species of cone snails; Conus vexillum, Conus fulgetrum, Conus flavidus, with no significant effect on the survival and motility of S. mansoni worms. In contrast, the muscle extract of Conus textile showed significant effect on the survival and motility of S. mansoni worms and the LD₅₀ was 43.85 μg/ml. However, the muscle extract of Conus lividus showed a weak effect (mortality rate 13%) on the viability and motility of S. mansoni worms at high concentration only (100μg/ml) after 96 hours of incubation. The probable tegumental alterations of worms after exposure to the muscle extracts were investigated using scanning electron microscopy (SEM). C. textile muscle extract could induce tegumental damage in S. mansoni worms, including the loss and damage of surface tubercles, as well as the destruction of oral sucker. It can also cause the development of protuberances and shortening of tegumental spines especially around the gynaecophoric canal. In conclusion, the current study revealed the schistosomicidal effect of C. textile muscle extract and might lead to novel antischistosomal drugs.