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Toxoplasma gondii is a ubiquitous, obligate intracellular parasite capable of crossing the placental barrier and causing spontaneous abortion, preterm labor, or significant disease in the surviving neonate. To better understand molecular mechanisms underlying abnormal pregnancy outcomes caused by T. gondii , placental proteins extracted from T. gondii -infected and -uninfected mice were comparatively analyzed using label-free liquid chromatography–tandem mass spectrometry. Significant difference was observed in the expression of 58 out of 792 proteins in infected placentas ( p < 0.05) compared with that in uninfected placentas. Quantitative real-time polymerase chain reaction, western blotting, and immunohistochemical staining were used to validate the results of the proteomic analysis. Some placental proteins differentially expressed in infected and uninfected mice were found to be associated with several different biological processes of pregnancy, particularly with trophoblast invasion and placental development. The results provide possible novel insights into the molecular mechanisms for abnormal pregnancy outcomes associated with T. gondii infection. Significance In order to further explore the mechanisms of abnormal pregnant outcomes caused by T. gondii infection, we first applied label-free proteomic technology to analyze the differentially expressed host placental proteins with T. gondii infection. The results showed that some differential proteins are associated with trophoblast invasion and placenta development. The findings provide a systemic view of the altered placental proteins and help to declare the molecular mechanisms of abnormal pregnancy outcomes caused by T. gondii infection. [ABSTRACT FROM AUTHOR]