Thiolated polymers or designated thiomers are gained by immobilization of sulhydryl-bearing ligands on the polymeric backbone of well established polymers, such as chitosan and poly(acrylates). This functionalization leads to significantly improved properties compared with the corresponding unmodified polymers. Mucoadhesive properties are strongly improved by the formation of disulfide bonds between thiol groups of the thiomer and cysteine-rich glycoproteins of the mucus gel layer. Moreover, enzyme- and efflux-pump inhibiting, as well as significantly improved permeation-enhancing properties, are advantages of polymer thiolization. Thiomer micro- and nano-particlulate delivery systems can be generated via different techniques, such as in situ gelation and subsequent covalent crosslinking, radical emulsion polymerization, emulsification/solvent evaporation or air jet milling. As thiomer micro- and nano-particles were shown to exhibit the same features as thiolated polymers per se, they might be useful tools for the delivery of various types of challenging drugs.