The present study investigates the role of Secreted Frizzled-Related Protein 2 (SFRP2) in trophoblast cells, a key factor in preeclampsia (PE) progression. Elevated levels of Secreted Frizzled-Related Protein 1/3/4/5 (SFRP1/3/4/5) are associated with PE, but the role of SFRP2 is unclear. We analyzed SFRP2 expression in PE placental tissue using the GSE10588 dataset and overexpressed SFRP2 in JEG-3 cells via lentiviral transfection. The viability, migration, apoptosis, and proliferation of SFRP2-overexpressing JEG-3 cells were assessed using Cell Counting Kit-8, Transwell assays, flow cytometry, and EdU staining. Additionally, we evaluated the impact of SFRP2 overexpression on key proteins in the Wnt/beta-catenin pathway and apoptosis markers (Bax, cleaved-caspase 3, BCL-2, MMP9, E-cadherin, Wnt3a, Axin2, CyclinD1, c-Myc, p-beta-catenin, beta-catenin, phosphorylated Glycogen Synthase Kinase 3 beta (p-GSK3 beta), and GSK3 beta) through western blotting. Results showed high SFRP2 mRNA and protein expression in PE placenta and JEG-3 cells post-transfection. SFRP2 overexpression significantly reduced JEG-3 cell viability, proliferation, and migration, while increasing apoptosis. It also altered expression levels of Wnt pathway proteins, suggesting SFRP2 ' s potential as a therapeutic target for PE by inhibiting trophoblast cell migration through the Wnt/beta-catenin signaling cascade.