Periodontitis is an infection-induced inflammatory disease characterized by progressive destruction of tooth supporting tissues, which, if left untreated, can result in tooth loss. The destruction of periodontal tissues is primarily caused by an imbalance between the host immune protection and immune destruction mechanisms. The ultimate goal of periodontal therapy is to eliminate inflammation and promote the repair and regeneration of both hard and soft tissues, so as to restore the physiological structure and function of periodontium. Advancement in nanotechnologies has enabled the development of nanomaterials with immunomodulatory properties for regenerative dentistry. This review discusses the immune mechanisms of the major effector cells in the innate and adaptive immune systems, the physicochemical and biological properties of nanomaterials, and the research advancements in immunomodulatory nanotherapeutic approaches for the management of periodontitis and the regeneration of periodontal tissues. The current challenges, and prospects for future applications of nanomaterials are then discussed so that researchers at the intersections of osteoimmunology, regenerative dentistry and materiobiology will continue to advance the development of nanomaterials for improved periodontal tissue regeneration.