Background: Praziquantel (PZQ) is the drug of choice recommended by the World Health Organization for the treatment and control of human schistosomiasis. The fact that schistosomes are developing resistance to PZQ indicates the urgent need for new effective treatment compounds. Herbal medicinal products, either as pure compounds or as standardized plant extracts, have been employed successfully for the development of new drugs. Limonin which is a citrus fruit compound has been reported to possess a wide range of biological activities. Aim of the work: To investigate in vitro the therapeutic efficacy of limonin as an alternative anti-schistosomal compound. Material and Methods: The in vitro assay was carried out on adult Schistosoma mansoni worms (Egyptian strain) using four concentrations of limonin in RPMI-1640 culture medium (15.6, 31.2, 62.5, 125.0 μg/mL). Schistosomes recovered from all groups were processed for ultrastructural investigation by scanning electron microscopy. Results: Limonin at a concentration of 125.0 μg/mL reduced the worm motor activity and caused death of all male schistosomes, which were more susceptible. The product had a concentration-dependent response effect within a smaller period of exposure. Female worms showed less prominent effects (death) at higher tested concentrations associated with reduction in the motor activity. This effect decreased with reduction of concentration . On the ultrastructural level, limonin at higher concentrations induced massive tegument destruction exposing the sub-tegument tissues. Conclusion: Obtained data confirm that limonin is effective against adult S. mansoni in vitro and presents a potential for the development of a candidate anti-parasitic agent.