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This review explores the pivotal roles of key immune cells (including mast cells, macrophages, neutrophils, T cells, B cells, and dendritic cells) in driving inflammatory progression and tissue damage through dynamic cellular interactions and cytokine networks. It systematically analyzes the molecular and structural foundations of immunomodulatory biomaterials, such as nanoparticles, hydrogels, and scaffolds, which offer precise spatiotemporal control over immune cell phenotypes and inflammatory mediators. By integrating advances in immunology and materials science, this review highlights how surface functionalization, controlled drug release, and composite material strategies synergistically restore immune homeostasis and promote tissue regeneration. Studies across common chronic inflammatory diseases (e.g., osteoporosis, osteomyelitis, osteoarthritis, diabetic wounds, spinal cord injury, and intervertebral disc degeneration) demonstrate the therapeutic potential of biomaterial\u2010mediated immunomodulation, such as nanoparticle\u2010driven macrophage polarization, cytokine\u2010loaded hydrogel\u2010mediated immune cell balance, and scaffold\u2010guided immune cell recruitment. Challenges in clinical translation, including material biocompatibility and multicomponent synergy, are critically addressed. 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