Scaffolds play an important role in bone tissue engineering. The ideal engineered scaffold needs to be biocompatible, bioactive, and able to regulate immune cells to enhance bone regeneration. In this study, magnesium (Mg)-contained poly(lactic-co-glycolic acid) (PLGA) scaffolds (hereinafter, referred to as PLGA-2Mg) were fabricated by 3-dimensional printing using a mixture of PLGA and MgSO4 powder. Poly(lactic-co-glycolic acid) scaffolds (hereinafter, referred to as PLGA) were also fabricated by 3-dimensional printing and were used as control. The biocompatibility, immunoregulatory ability, and osteogenic properties of PLGA-2Mg were analyzed and compared with those of PLGA. The results indicate that the incorporation of Mg increased the Young modulus and surface roughness of the scaffold, but did not affect its degradation. The PLGA-2Mg further promoted the adhesion and proliferation of MC3T3-E1 cells compared with PLGA, which indicates its improved biocompatibility and bioactivity. In addition, PLGA-2Mg inhibited the polarization of RAW 264.7 cells toward the M1 phenotype by down-regulating the IL-1β, IL-6, and iNOs gene expression when challenged with lipopolysaccharide stimulation. In contrast, it promoted the polarization of RAW 264.7 cells toward the M2 phenotype by up-regulating the TGF-β, IL-10, and Arg-1 gene expression without lipopolysaccharide stimulation. Finally, MC3T3-E1 cells were cocultured with RAW 264.7 cells and scaffolds using a transwell system. It was found that the expression level of osteogenic-related genes (ALP, COL-1, BMP2, and BSP) was significantly upregulated in the PLGA-2Mg group compared with that in the PLGA group. Consequently, PLGA-2Mg with increased biocompatibility and bioactivity can promote osteogenesis through immunoregulation and has the potential to be used as a novel scaffold in bone tissue engineering.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Mutaz B. Habal, MD.