Interaction in solution and in the solid state of triclosan (TR), a practically water-insoluble antimicrobial agent, with parent β-cyclodextrin (βCD) and its water-soluble epichlorohydrin polymer (EPI-βCD) was investigated by several analytical techniques, to evaluate the role of the carrier features on the physicochemical properties of the drug-cyclodextrin complex. Phase-solubility studies showed the higher solubilizing and complexing ability of EPI-βCD (K(s) =1 1,733 M(-1)) than parent βCD (K(s) = 2526 M(-1)). Actual inclusion complex formation between TR and both cyclodextrins tested was confirmed by 2D (1)H NMR studies (ROESY), which also gave insight into some different drug/cyclodextrin binding modes between polymeric and parent βCD. Addition of hydrophilic polymers (hydroxypropylcellulose, hypromellose or amidated pectin) to TR/βCD systems increased βCD solubilizing efficacy, but, unexpectedly, decreased its complexing ability towards the drug. Solid binary and ternary samples prepared by co-grinding of components in high energy mills were carefully characterised by Differential Scanning Calorimetry, X-ray powder diffractometry and Fourier transform infrared spectroscopy. The results pointed out the higher affinity of EPI-βCD than βCD for the interaction with TR even in the solid state, resulting in the formation of completely amorphous products with superior dissolution properties. Addition of hydrophilic polymers failed to effectively promote solid-state interactions between TR and βCD, while their positive influence on drug solubility, observed in phase-solubility studies, was absent in solid TR/βCD/polymer products. Finally, the time-kill analysis, used to evaluate the TR antimicrobial activity against Streptococcus mutans, demonstrated the significantly (p < 0.001) superior performance of both cyclodextrin complexes than drug alone, and confirmed the higher effectiveness (p < 0.05) of TR/EPI-βCD than TR/βCD complex.