Ideal coating materials for implants should be able to induce excellent osseointegration, which requires several important parameters, such as good bonding strength, limited inflammatory reaction, and balanced osteoclastogenesis and osteogenesis, to gain well-functioning coated implants with long-term life span after implantation. Bioactive elements, like Sr, Mg, and Si, have been found to play important roles in regulating the biological responses. It is of great interest to combine bioactive elements for developing bioactive coatings on Ti-6Al-4 V orthopedic implants to elicit multidirectional effects on the osseointegration. In this study, Sr-, Mg-, and Si-containing bioactive Sr2MgSi2O7 (SMS) ceramic coatings on Ti-6Al-4 V were successfully prepared by the plasma-spray coating method. The prepared SMS coatings have significantly higher bonding strength (∼37 MPa) than conventional pure hydroxyapatite (HA) coatings (mostly in the range of 15-25 MPa). It was also found that the prepared SMS coatings switch the macrophage phenotype into M2 extreme, inhibiting the inflammatory reaction via the inhibition of Wnt5A/Ca(2+) and Toll-like receptor (TLR) pathways of macrophages. In addition, the osteoclastic activities were also inhibited by SMS coatings. The expression of osteoclastogenesis-related genes (RANKL and MCSF) in bone-marrow-derived mesenchymal cells (BMSCs) with the involvement of macrophages was decreased, whereas OPG expression was enhanced on SMS coatings compared to HA coatings, indicating that SMS coatings also downregulated the osteoclastogenesis. However, the osteogenic differentiation of BMSCs with the involvement of macrophages was comparable between SMS and HA coatings. Therefore, the prepared SMS coatings showed multidirectional effects, such as improving bonding strength, reducing inflammatory reaction, and downregulating osteoclastic activities, but maintaining a comparable osteogenesis, as compared with HA coatings. The combination of bioactive elements of Sr, Mg, and Si into bioceramic coatings can be a promising method to develop bioactive implants with multifunctional properties for orthopedic application.