Background. Schistosomiasis is caused by parasitic flatworms and the disease is endemic to most countries in sub-Saharan Africa including Ghana. The current therapeutic agent for managing this disease solely relies on praziquantel. The continual dependence on this single available drug could lead to possible drug resistance. This study seeks to evaluate the antischistosomal activity of the following Ghanaian medicinal plants: Khaya senegalensis, Vernonia amygdalina, Clausena anisata, and Bridelia ferruginea. Methodology. Two concentrations (100 μg/mL and 50 μg/mL) of each extract were tested in a 96-well plate containing 30 newly transformed schistosomula (NTS). Moreover, six worms of both sexes of adult Schistosoma mansoni were exposed to the extracts diluted in the RPMI medium. The assay was performed in a 24-well plate. The parasitic worms were examined using an inverted optical microscope. Results. At 100 μg/mL and 50 μg/mL, all extracts performed better and showed strong activity (p<0.001) against NTS; thus, 98.08%, 100%, 80.77%, and 100% for Clausena, Vernonia, Bridelia, and Khaya, respectively, when compared to praziquantel. Strong activity was recorded when the extracts underwent testing against Schistosoma mansoni adults at 100 μg/mL; 96.35%, 100%, and 94.55% for Vernonia, Bridelia, and Khaya, respectively, except for Clausena which exhibited weak activity, i.e., 56.02%. There was no significant difference between Vernonia, Bridelia, and Khaya when compared to praziquantel. Conclusion. At 100 μg/mL, Khaya senegalensis, Vernonia amygdalina, and Bridelia ferruginea extracts demonstrated strong activity against both schistosomula and adult Schistosoma mansoni. These data can serve as baseline information in the quest to find alternative therapeutic agents to treat schistosomiasis.