Phytoestrogens have recently been receiving more attention as a promising therapeutic agent for the prevention of bone loss in postmenopausal osteoporosis. Curcuma comosa Roxb. (C. comosa) is a ginger-family plant containing phytoestrogens and has been used extensively as dietary supplement to relieve menopausal symptoms. Diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD), isolated from C. comosa, was identified as the active phytoestrogen. DPHD has previously been found to activate Wnt/β-catenin signaling to increase differentiation in transformed mouse osteoblasts. However, its effect on human bone cells has not been reported. In the present study, we investigated the osteogenic effect and mechanism of action of DPHD in nontransformed human osteoblasts (h-OB). In growth medium, DPHD increased h-OB proliferation, investigated by thymidine incorporation assay and it accelerated osteoblast differentiation in the differentiation medium as indicated by the increases in alkaline phosphatase activity and osteoblast-specific mRNA production at 7-21 days. The effects of DPHD were abolished by estrogen receptor antagonist ICI182780. During the differentiation, DPHD promoted early expression of osteoblast transcription factors; RUNX2 and osterix. Subsequently, DPHD accelerated production of bone structural genes, including collagen type I alpha I (COL1A1) and osteocalcin comparable to 17β-estradiol. Moreover, DPHD increased the osteoprotegerin to RANKL ratio indicated that it could promote osteoblast bone formation. It was supported by the increased bone mineralization of DPHD detected by Von kossa staining. In conclusion, DPHD effectively promotes human osteoblast proliferation, differentiation and mineralization. The stimulating effects of the phytoestrogen from C. comosa on human osteoblasts may have clinical relevance for assisting in maintenance of bone mass menopausal women.