<p>Iron deficiency is the most prevalent nutritional disorder globally. Conventional treatment primarily involves oral supplementation with various iron salts, such as ferrous sulfate. While cost-effective and easily administered, these salts are associated with several challenges, including gastrointestinal irritation, prolonged treatment duration, and poor patient compliance due to adverse side effects. To address these limitations, nanotechnology has been employed to develop improved oral iron supplements with varying degrees of success. Utilizing approaches from nanotechnology and materials science, researchers have engineered diverse iron-containing nanomaterials designed to provide bioavailable iron. However, the efficacy of these nanomaterials as oral supplements is highly dependent on their specific physicochemical properties. An effective nano-based replacement for iron salts must exhibit high bioavailability for efficient iron restoration and low toxicity to minimize side effects. This review consolidates in vivo research on various iron nanomaterials evaluated as oral iron supplements. Furthermore, it proposes a framework for the ideal characteristics of an oral iron nanoparticle supplement by consolidating the current understanding of the mechanisms governing nanoparticle absorption and toxicity.</p>