The aim of the present study was to investigate the antiosteoclastogenic effects of black rice ( Oryza sativa L.) fermented with Lactobacillus casei (LAB) in RANKL-induced RAW macrophage cells and its antiosteoporosis activity against ovariectomy-induced osteoporosis in rats. LAB extract (LABE) treatment attenuated receptor activator of nuclear factor-kappa B (NF- κB) ligand-induced osteoclastic differentiation in RAW cells by inhibiting intercellular reactive oxygen species generation and downregulating the activation of mitogen-activated protein kinases and NF- κB, leading to the downregulation of c-Fos and expression of nuclear factor of activated T cells c1. This consequently suppressed the expression of osteoclast-specific genes including those for cathepsin K, tartrate-resistant acid phosphatase, calcitonin receptor, and integrin β3. Oral administration of LABE protected against ovariectomy-induced bone loss by significantly inhibiting bone architecture alterations and improving serum bone turnover markers in ovariectomized rats. The findings suggest that the antiosteoporotic activity of LABE may be derived from its antiosteoclastic and anti-bone-resorptive activities. LABE has potential as a promising functional material or substrate to prepare protective agents for osteoporosis and osteoclast-mediated bone diseases.