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Macrophage polarization is an essential process involved in immune regulation. In response to different microenvironmental stimulation, macrophages polarize into cells with different phenotypes and functions, most typically M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages. Iron-based nanoparticles have been widely explored and reported to regulate macrophage polarization for various biomedical applications. However, the influence factors and modulation mechanisms behind are complicated and not clear. In this review, we systemically summarized different iron-based nanoparticles that regulate macrophage polarization and function and discussed the influence factors and mechanisms underlying the modulation process. This review aims to deepen the understanding of the modulation of macrophage polarization by iron-based nanoparticles and expects to provide evidence and guidance for subsequent design and application of iron-based nanoparticles with specific macrophage modulation functions.