The aim of this study was to identify the best combination of chlorhexidine (CHX) with orthodontic elastomerics for prevention of oral disease in orthodontic patients. We used ethyl cellulose (EC) as the polymer, and experimental groups were divided into five groups according to differences in solvent (i.e., ethanol; EtOH, dichloromethane; DCM). CHX release from the coated elastomerics was evaluated with a UV spectrophotometer and observed by scanning electron microscope (SEM). The antimicrobial release increased over time for 48 h in Group 3 (CDA+EC+30% EtOH/70% DCM), exhibiting the longest sustained-release characteristics (p<0.001). It also showed the highest antimicrobial properties, which was confirmed by inhibition zone testing using S. mutans (p<0.05). All groups were not affected when tensile force was tested in the coated elastomerics. We conclude that the antibacterial effect of CHX can be adjusted according to combinations of polymers and solvents. Group 3 exhibited the best substantivity and antimicrobial properties.