Poly(methyl methacrylate) (PMMA) bone cement has been widely used in orthopedic surgeries including total hip/knee r. replacement, vertebral compression fracture treatment, and bone defect filling. However, aseptic loosening of the interface between PMMA bone cement and bone often leads to failure. Hence, the development of modified PMMA that facilitates the growth of bone into the modified PMMA bone cement is key to reducing the incidence of aseptic loosening. In this study, MgAl-layered double hydroxide (LDH) microsheets modified PMMA (PMMA&LDH) bone cement with superior osseointegration performance has been synthesized. The maximum polymerization reaction temperature of PMMA&LDH decreased by 7.0 and 11.8 degrees C, respectively, compared with that of PMMA and PMMA&COL-I (mineralized collagen I modified PMMA). The mechanical performance of PMMA&LDH decreased slightly in comparison with PMMA, which is beneficial to alleviate stress-shielding osteolysis, and indirectly promote osseointegration. The superior osteogenic ability of PMMA&LDH has been demonstrated in vivo, which boosts bone growth by 2.17- and 18.34-fold increments compared to the PMMA&COL-I and PMMA groups at 2 months, postoperatively. Moreover, transcriptome sequencing revealed four key osteogenic pathways: p38 MAPK, ERK/MAPK, FGF, and TGF-beta, which were further confirmed by IPA, qPCR, and Western blot assays. Hence, LDH-modified PMMA bone cement is a promising biomaterial to enhance bone growth with potential applications in relevant orthopedic surgeries.