Fibrinogen-like (Fgl2) protein belongs to fibrinogen super family, which catalyzes the conversion of prothrombin to thrombin and is involved in the coagulation process. There are two different forms of functional Fgl2 protein: membrane associated Fgl2 (mFgl2) and soluble Fgl2 (sFgl2). mFgl2, as a type II transmembrane protein with property with prothrombinase activity from its N-terminal fragment, was extensively secreted or expressed by inflammatory macrophages, dendritic cells (DCs), Th1 cells and endothelial cells. While sFgl2 was mainly produced by regulatory T cells (Tregs) and then secreted into the vasculature, which contributes to autoimmune disease by regulating maturation of (DCs), polarization of macrophage, inhibiting T cell proliferation and differentiation and inducing apoptosis of B cells. In particular, emerging evidence has shown that Fgl2 is implicated in female reproductive system that contributes to embryo development, ovarian granulosa cells differentiation and implantation failure. This article summarizes the role and potential mechanisms of Fgl2 in reproduction and identifies research gaps along with the future directions.