Tightly regulated trophoblast invasion and immunomodulation at the feto-maternal interface is important during implantation and fetal development. Although trophoblasts as a pregnancy-specific cell has been reported to be a key factor capable of regulating certain events during implantation, however, its regulatory mechanisms are still unclear. In this study, we analyzed the effects of chorionic plate-derived mesenchymal stem cells (CP-MSCs) and human placenta extract (hPE) isolated from human normal placentas on trophoblasts invasion and immune responses. We investigated the effects of CP-MSCs, hPE treatment, and their combination on trophoblasts invasion and on T-cells suppression through human leukocyte antigen-G (HLA-G) expression. Trophoblasts invasion was significantly increased by co-culture of CP-MSCs or by hPE treatment (P<0.05), and enhanced by the combination of CP-MSCs and hPE treatment (P<0.05). The proliferation of T-cells was decreased by co-culture of CP-MSCs and hPE treatment, whereas the population of regulatory T-cells was increased (P<0.05). Also, the dynamics alterations of multiple cytokines were observed in the culture supernatants of trophoblasts and T-cells depending on CP-MSCs co-culture and hPE treatment. Interestingly, the concentration of soluble HLA-G was increased by CP-MSCs co-culture, by hPE treatment and by combination of them on trophoblasts and activated T-cells (P<0.05). These findings suggested that CP-MSCs and hPE can regulate trophoblasts invasion and T-cell by alteration of HLA-G expression. These results will provide understandings of trophoblasts invasion and the immunological network at the feto-maternal interface during pregnancy and contribute to the foundation of a new treatment strategy for pregnancy disorders.