The present investigation was aimed to evaluate the protective and therapeutic effect of Fagonia critica extract (FCE) against Bisphenol A (BPA) induced genotoxicity and histopathology in rats. Genetic study included expression of P450 aromatase and Tph2 genes in the brain tissues in addition to expression of P450 aromatase and COX-1 genes in testis tissues. Histological examination was documented in each of the brain and testis tissues. Our results demonstrated that the exposure to BPA had induced over-expressions of above genes and produced massive damage in histological architectures of brain and testis cells. Treatment with different doses (3.3 g/kg; 4.2 g/kg and 5.0 g/kg) of FCE in BPA-intoxicated rats markedly reduced the genotoxicity and histopathology parameters. These improvements increased by increasing the dose of FCE as a protective or therapeutic agent. Best results were found through utilization FCE as a therapeutic agent, especially by using the highest dose (5.0 g/kg), in which some genotoxic and histopathology parameters had been relatively restored towards the normal level or natural status. This study proved that the treatment with FCE has the capability for alleviating and facing BPA genotoxicity and histopathology. Since the treatment with extraction of this medicinal plant succeeded in overcoming BPA-induced over-expression of P450 aromatase, Tph2 and COX-1 genes, modulating them to approximately normal values and mitigating BPA histopathology status.