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There is evidence to suggest that restoration of major/rare biominerals by supplementation can produce osteogenic and anti-resorptive effects in humans. LithoLexal^® is a natural extract harvested from a marine alga, <i>Lithothamnion</i> sp., with a porous microstructure and multimolecular composition rich in calcium (32% <i>w</i>/<i>w</i>) and magnesium (2.2% <i>w</i>/<i>w</i>) together with ~72 trace bioelements. In vitro, LithoLexal^® demonstrated cellular-level osteogenic efficacy through enhancing the maturation and activity of pre-osteoblasts. This extract also expressed the ability to suppress osteoclastogenesis by downregulating the pro-resorptive cytokines TNF-α and IL-1β and the master regulator of inflammation NF-κB. Parathyroid hormone inhibition of parathyroid hormone secretion is another bioactivity of LithoLexal^® Bone reported with both short- and long-term administration at a longer duration and higher magnitude than what calcium carbonate could induce. Due to these bioactivities that affect pathogenetic factors of osteoporosis, LithoLexal^® Bone is referred to as a disease-modifying adjunctive therapy (DMAT). In postmenopausal animal models, LithoLexal^® monotherapy preserved bone mineral density, microarchitecture, and biomechanical properties, while calcium carbonate failed to produce significant outcomes. The pro-resorptive effect of a high-fat diet was also efficiently counteracted in vivo by supplementary LithoLexal^®. A large clinical trial on postmenopausal women verified the mitigating effects of LithoLexal^® Bone on bone resorption and turnover rate. The characteristic composition of LithoLexal^® together with its lattice microstructure are suggested to underlie its in vivo bioactivities. In conclusion, adjunctive therapy with LithoLexal^® Bone is an attractive option for clinical prevention and treatment of osteopenia/osteoporosis.