Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge. This study used magnesium silicate nanospheres (MSNs) loaded with microRNA-146a-5p (miR-146a) to fabricate MSN+miR-146a, a nanobiomaterial that synergistically promoted osteogenic differentiation of human dental pulp stem cells (hDPSCs). miR-146a exhibited anti-inflammatory effects on macrophages by inhibiting the NF-κB pathway, while MSNs promoted M2 macrophage polarization. miR-146a also inhibited osteoclast formation. In a mouse model, MSN+miR-146a, delivered via a photocuring hydrogel, showed dual osteogenic-promoting and immunoregulatory effects, suggesting its potential for treating inflammatory bone defects.