Progression of Prostatic Intra-epithelial Neoplasia (PIN) to Prostate Cancer (PCa) is characterized by a long latency period. This presents several opportunities for intervention. G-Protein coupled Estrogen Receptor 1 (GPER1) has emerged as an attractive target in the field of oncology. Existing data suggest that GPER1 activation inhibits PCa growth. However, the potential of GPER1 as a target for PCa chemoprevention remains unexplored. Analysis of publicly available datasets revealed a significant reduction in the prostatic GPER1 expression in the advanced PCa cases, compared to non-cancerous prostates. This was corroborated by our investigations of human primary PCa samples and the TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mouse model. The frequency of GPER1-positive cells and the expression of GPER1 were significantly higher in the TRAMP prostates presenting High-Grade PIN (HGPIN), compared to control prostates. However, this pattern reversed as HGPIN progressed to PCa. Activation with G1 (an agonist of GPER1) at the HGPIN stage prevented the progression of HGPIN to PCa in TRAMP mice. This effect was abrogated by co-administration of G1 with G15 (an antagonist of GPER1). In vitro activation with G1 inhibited proliferation in LNCaP, PC3, and RWPE-1 cell lines. On the other hand, GPER1-silencing led to a significant increase in in-vitro migration, invasion, and epithelial to mesenchymal transition through miR200a-ZEB2-E-Cadherin loop and by dysregulating the expression of metastasis-associated genes. These observations collectively suggest that GPER1 has a protective role in the context of PCa. Human studies are warranted to assess the potential of GPER1 as a target for PCa chemoprevention.