Toxoplasma gondii (T. gondii) infection in female mammals during pregnancy can result in poor pregnancy. Similarly, it can result in male reproductive disorders in male mammals. Although the testes and uterus have very different biological makeup, they are still both attacked by T. gondii resulting in reproductive dysfunctions. We hypothesized that there are significant common genes in the testes and uterus that interact with T. gondii. Finding out and studying these genes is vital to understand the infection mechanism of T. gondii and the induced disease pathogenesis. To achieve this goal, we built a mice model of acute infection with T. gondii and the testes and uterus of the mice were sequenced by RNA-Seq. A total of 291 and 679 significantly differently expressed genes (DEGs) were obtained from the testes and the uterus, respectively. In the Gene Ontology (GO) analysis, part of the DEGs in the testes and uterus were related to 35 GO functions. When compared with the KEGG database, seven pathways affecting both the testes and uterus during the course of T. gondii infection were identified. In addition, Toxoplasmosis can significantly affect the expression of Nlrp5 and Insc leading to negative outcomes in the host. On the other hand, the host regulates Gbp7, Gbp2b, and Ifit3 to defend against T. gondii infection.