Poly(methyl methacrylate) (PMMA) bone cements have been widely used in clinical practices. In order to enhance PMMA’s imaging performance to facilitate surgical procedures, a supplementation of radiopaque agent is needed. However, PMMA bone cements are still facing problems of loosening and bacterial infection. In this study, a multifunctional coating to simultaneously encapsulate drug and prevent the infection of radiopaque agent has been developed. Barium sulfate (BaSO4), a common radiopaque agent, is used as a substrate material. We successfully fabricated porous BaSO4 microparticles, then modified with hexakis-(6-iodo-6-deoxy)-alpha-cyclodextrin (I-CD) and silver (Ag) to obtain porous BaSO4@PDA/I-CD/Ag microparticles. The porous nature and presence of PDA coating and I-CD on the surface of microparticles result in efficient loading and release of drugs such as protein. Meanwhile, the radiopacity of BaSO4@PDA/I-CD/Ag microparticles is enhanced by this multifunctional coating containing Ba, I and Ag. PMMA bone cements containing BaSO4@PDA/I-CD/Ag microparticles show 99% antibacterial rate against both Staphylococcus aureus (S. aureus) and Escherichia Coli (E. coli), yet without apparently affecting its biocompatibility. Together, this multifunctional coating possessing enhanced radiopacity, controlled drug delivery capability and exceptional antibacterial performance, may be a new way to modify radiopaque agents for bone cements.