Synthetic polymers, polyacrylic acid (PAA) and polyallylamine (PAAm), were thiolated using different methods of thiolation. Both polymers resulted in comparable thiol contents, thus allowing for the direct comparison of mucoadhesive and cohesive properties between the well-established thiolated PAA and the more novel thiolated PAAm. Thiolation of both polymers improved the swelling ability and the cohesive and mucoadhesive properties in comparison to unmodified control samples. In this study, it was shown that the swelling abilities of the thiolated PAAm sample were far greater than that of the thiolated PAA sample which, in turn, affected the drug release profile of the thiolated PAAm sample. Importantly, however, the mucoadhesive properties of thiolated PAAm were equivalent to that of the thiolated PAA sample as demonstrated by both the adhesion times on porcine intestinal tissue as measured by the rotating cylinder method and by rheological studies with a mucin solution. This study demonstrates the potential thiolated polyallylamine has as a mucoadhesive drug delivery device.