Nanosized polyphosphate bodies (PPB) are potential iron supplements for iron deficiency treatment, which can be produced by microalgal cell factories. To investigate the effect of PPB on iron-deficiency anemia, iron-deficient rats were constructed and given feeds with different iron supplements. Four iron supplements, i.e. PPB from microalgae, FeSO4, ferric citrate (FC), and synthetic polyphosphate (PolyP) + FC, were investigated in iron-deficiency anemia treatment at three different dietary intervention stages (i.e. day 3, 7, and 10). These four iron supplements showed similar hemoglobin (Hb) improvements at day 3 and 7, respectively; however, PPB and FeSO4 resulted in higher increased Hb and reticulocyte Hb than FC and PolyP at day 10. The Hb regeneration efficiencies followed the order: PolyP (42.6%) ≈ FC (47.7%) < FeSO4 (56.1%) ≈ PPB (56.2%). The absolute reticulocyte content increased from day 3 to day 7 then decreased at day10 in all iron repletion groups. PPB diet supplied more intestinal total soluble, low-molecular weight, and nanosized iron than FC and PolyP diets. Overall, PPB are novel natural iron supplements that can be used for iron-deficiency anemia treatment, opened new possibilities to develop natural microalgal nanoparticles as high-value products in human health improvement.