Abstract: Background: Schistosomiasis is contracted by exposure to fresh water containing cercariae that develop into adult worms after penetration of human skin. Interruption of schistosomiasis vital cycle by elimination of cercariae may enhance methods of transmission control. Objective: To evaluate the vitro effect of methanol extracts of Solanum nigrum ( S.nigrum) and callistemon citrinus (C. citrinus) leaves on Schistosoma mansoni cercarial genetic makeup by random amplification of polymorphic DNA-Polymerase chain reaction (RAPD-PCR). Material and methods: The effect different concentrations of both plants extracts on cercarial morphology and mortality was observed with different lethal concentrations (LC). Also, assessment of DNA change in exposed S.mansoni cercariae to LC50 of both plants in comparsion with non-exposed ones by RAPD-PCR assay was investigated. Cercariae were divided into three groups: group A: control non-exposed cercariae; group B: cercariae exposed to S.nigrum; and group C: cercariae exposed to C.citrinus. Results: The cercaricidal potency of tested extracts was concentration-dependent. The cercaricidal toxicity of S. nigrum extracts was 1.2 times higher than that of C.citrinus(LC90 values were 50 mg/L and 60 mg/L, respectively). RAPD-PCR revealed different band polymorphism patterns for each primer used and cercariae exposed to S.nigrum revealed a higher number of band polymorphism (20 bands) than that obtained by cercariae exposed to C.citrinus (16 bands) which were different from those of control group reflecting the genetic variability among the groups studies. Conclusion: C.citrinus and S.nigrum are effective cercaricidal agents that can be utilized to minimize water transmission of schistosomiasis. Also, RAPD-PCR is useful for examining the genetic polymorphism of schistosomal cercariae induced by plants extracts, and assessment of genetic of damage of drug development fields.