Nanostructured iron(III) compounds are promising food fortificants with desirable iron bioavailability and food compatibility. Here, gum arabic (GA) solubilized 252 mg of iron(III) per g at neutral pH in the form of GA-stabilized ferric oxyhydroxide nanoparticles (GA-FeONPs) with Z-average size of 142.7 ± 5.9 nm and ζ-potential of −20.50 ± 1.25 mV. Calceinfluorescence-quenching assay revealed well-absorbed iron from GA-FeONPs by polarized Caco-2 cells due to efficient macropinocytic internalization and asialoglycoprotein receptor-mediated specific endocytosis facilitated by the polypeptide and arabinogalactan fractions of GA, respectively, with endocytosed GA-FeONPs being in part basolaterally transcytosed and in another part degraded into cellular labile iron pool. GA-FeONPs showed good colloidal stability under varied pH, gastrointestinal, thermal processing, and spray/freeze drying conditions and displayed remarkably weaker pro-oxidant activity than FeSO 4 in glyceryl trilinoleate emulsion (P < 0.05). Oral pharmacokinetics unveiled desirable iron bioavailability of GA-FeONPs relative to FeSO 4 , i.e., 124.27 ± 5.91% in aqueous solution and 161.64 ± 5.01% in milk. Overall, GA-FeONPs are a promising novel iron fortificant with food-compatible, efficient, and targeted intestinal iron delivery and sustained iron-release properties.