Hormone deficiency has been recognized as a risk factor for periodontal disease in postmenopausal women. However, the anabolic effects of progesterone on human periodontal ligament cells (hPDLCs) are still unclear. Therefore, the objective of this study was to detect the expression of progesterone receptor (PgR) in hPDLCs and investigate the bone-sparing effects of progesterone. We detected PgR expression in hPDLCs by reverse transcriptase-polymerase chain reaction and immunocytochemistry. After progesterone stimulation, the percentage of hPDLCs entering the S + G2M phase of the cell cycle increased significantly, accompanied by an increased cell growth curve. In both basic culture medium and osteogenic medium, progesterone activated alkaline phosphatase-positive cells and alizarin red-positive nodules. Moreover, mineralization-related markers were up-regulated by progesterone in both time-dependent and dose-dependent manners. In contrast, these effects of progesterone were blocked by the PgR antagonist (RU486). Our results demonstrated that the PgR is expressed in hPDLCs at the gene and protein level, and that progesterone can stimulate the proliferation and differentiation of the hPDLCs. These findings suggest that progesterone may play a significant role in osteoblastic function of hPDLCs and may influence the maintenance of alveolar bone mass.