Rapid maxillary expansion (RME) is an effective approach for addressing maxillary transverse deficiency; however, it is prone to recurrence owing to insufficient bone remodeling within the maxilla midpalatal suture (MPS). Clinically established drug therapies or auxiliary interventions capable of reliably promoting osteogenesis in RME remain absent. As a potent antioxidant, selenium can decrease reactive oxygen species (ROS) production to influence bone metabolism and formation to promote remodeling. In this study, we propose the application of lentinan-engineered selenium nanoparticles (LET-SeNPs) in RME to accelerate bone formation in MPS. The results demonstrate that LET-SeNPs are capable of enhancing the proliferative capacity of rat bone marrow mesenchymal stem cells (rBMSCs) and facilitating their osteogenic differentiation. Furthermore, LET-SeNPs eliminate ROS via the thioredoxin/thioredoxin reductase 1 (Trx1/TrxR1) system and suppress oxidative stress, thereby augmenting the antioxidant capacity of rBMSCs. In a rat RME model, local injection of LET-SeNPs can accelerate bone formation in MPS by enhancing osteoblast activity and inhibiting osteoclast expression while simultaneously accelerating new bone maturation in MPS. In conclusion, the results of this study suggest that local injection of LET-SeNPs is a promising therapeutic intervention for improving the therapeutic efficacy of RME.