In the current study, bioavailability and biocompatibility of iron oxide–hydroxide (FeOOH) nanospheres (FeNSs) and nanorods (FeNRs) were compared in an in vivo study to investigate the impact of particles shape on efficacy of nano-based iron supplements. FeNSs and FeNRs were fabricated via bio-assisted synthesis reactions using secretory compounds from an edible microalga, Chlorella vulgaris. Resulted FeNSs were ~ 12.7 nm in mean diameter. Mean width of FeNRs were calculated to be 10.8 nm and their mean length was 56.1 nm. Rats were supplemented daily with FeOOH nanostructures and ferrous sulfate. After 1 month, hematologic parameters, serum and organs iron contents, liver function, and organ indexes were evaluated. FeNSs and FeNRs provided significantly increased levels for RBC, liver iron, and spleen iron in contrast to ferrous sulfate. However, just FeNRs were more efficient than ferrous sulfate to elevate the level of Hb (21.9% more than FeSO₄) and HTC (22.9% more than FeSO₄). It is considered that all examined iron supplements provide an equal level of serum iron. FeOOH nanostructures had no significant effect on toxicological parameters. The only point of concern was increased LDH levels in relation to FeNRs, about 6.4-fold increase was recorded in contrast to untreated group. However, no significant histopathological alterations were detected in FeNRs-treated animals. It can be concluded that nano-based iron supplements are significantly more efficient than iron salts, and the shape of nanostructures can affect their bioavailability. These data can pave the way for future studies toward more efficient and less toxic nano-based iron supplements.