AimsThis study aimed to investigate the anti‐inflammatory and odontoblastic effects of cerium‐containing mesoporous bioactive glass nanoparticles (Ce‐MBGNs) on dental pulp cells as novel pulp‐capping agents.MethodologyCe‐MBGNs were synthesized using a post‐impregnation strategy based on the antioxidant properties of Ce ions and proposed the first use of Ce‐MBGNs for pulp‐capping application. The biocompatibility of Ce‐MBGNs was analysed using the CCK‐8 assay and apoptosis detection. Additionally, the reactive oxygen species (ROS) scavenging ability of Ce‐MBGNs was measured using the 2,7‐Dichlorofuorescin Diacetate (DCFH‐DA) probe. The anti‐inflammatory effect of Ce‐MBGNs on THP‐1 cells was further investigated using flow cytometry and quantitative real‐time polymerase chain reaction (RT‐qPCR). Moreover, the effect of Ce‐MBGNs on the odontoblastic differentiation of the dental pulp cells (DPCs) was assessed by combined scratch assays, RT‐qPCR, western blotting, immunocytochemistry, Alizarin Red S staining and tissue‐nonspecific alkaline phosphatase staining. Analytically, the secretions of tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) were detected with enzyme‐linked immunosorbent assay (ELISA).ResultsCe‐MBGNs were confirmed to effectively scavenge ROS in THP‐1‐derived macrophages and DPCs. Flow cytometry and RT‐qPCR assays revealed that Ce‐MBGNs significantly inhibited the M1 polarization of macrophages (Mφ). Furthermore, the protein levels of TNF‐α and IL‐1β were downregulated in THP‐1‐derived macrophages after stimulation with Ce‐MBGNs. With a step‐forward virtue of promoting the odontoblastic differentiation of DPCs, we further confirmed that Ce‐MBGNs could regulate the formation of a conductive immune microenvironment with respect to tissue repair in DPCs, which was mediated by macrophages.ConclusionsCe‐MBGNs protected cells from self‐produced oxidative damage and exhibited excellent immunomodulatory and odontoblastic differentiation effects on DPCs. As a pulp‐capping agent, this novel biomaterial can exert anti‐inflammatory effects and promote restorative dentine regeneration in clinical treatment. We believe that this study will stimulate further correlative research on the development of advanced pulp‐capping agents.