Calcium is an essential mineral to support bone health and serves as a major therapeutic intervention to prevent and delay the incidence of osteoporosis. Many individuals do not obtain the optimum amount of calcium from diets and depend on bioavailable calcium supplements. The present study was conducted to examine the effect of a novel plant-based calcium supplement, derived from marine algae, and contains high levels of calcium, magnesium, and other bone supporting minerals [commercially known as AlgaeCal (AC)], on proliferation, mineralization, and oxidative stress in cultured human osteoblast cells, and compared with inorganic calcium carbonate and calcium citrate salts. Cultured human fetal osteoblast cells (hFOB 1.19) were treated with AC (0.5 mg/ml, fixed by MTT assay), calcium carbonate, or calcium citrate. These cells were harvested after 4 days of treatment for ALP activity, PCNA expression, and DNA synthesis, and 2 days for Ca(2+) deposition in the presence and absence of vitamin D3 (5 nM). The ability of AC to reduce H(2)O(2) (0.3 mM)-induced oxidative stress was assessed after 24 h of treatment. ALP activity was significantly increased with AC treatment when compared to control, calcium carbonate, or calcium citrate (4.0-, 2.0-, and 2.5-fold, respectively). PCNA expression (immunocytochemical analysis), DNA synthesis (4.0-, 3.0-, and 4.0-fold, respectively), and Ca(2+) deposition (2.0-, 1.0-, and 4.0-fold, respectively) were significantly increased in AC-treated cells when compared with control, calcium carbonate, or calcium citrate treatment. These markers were further enhanced following additional supplementation of vitamin D3 in the AC-treated group cells. AC treatment significantly reduced the H(2)O(2)-induced oxidative stress when compared to calcium carbonate or calcium citrate (1.5- and 1.4-fold, respectively). These findings suggest that AC may serve as a superior calcium supplement as compared to other calcium salts tested in the present study. Hence, AC may be developed as a novel anti-osteoporotic supplement in the near future.