Osteoporosis is an age-related disorder with enormous public health burden with an urgent need for better diagnosis and treatment. Herein, we have investigated the potential role of jatrorrhizine, a plant bioactive, in osteoporosis since it is known to exhibit a wide array of biologic and pharmacologic activities. Using MC3T3-E1 cells, a clonal murine cell line ofimmature osteoblasts derived from mice, we examined the effect of jatrorrhizine on various parameters of cell function. While jatrorrhizine exhibited no effect on MC3T3-E1 cell viability, it caused reversal of dexamethasone-induced suppression of calcium deposition and alkaline phosphatase activity, elevation of osteogenic differentiation related proteins, and decrease in the level of histone deacetylase 4. These observations led us to conclude that jatrorrhizine ameliorates osteogenic differentiation in dexamethasone treated MC3T3-E1 cells via histone deacetylase 4 suggesting its potential application in the treatment of osteoporosis.