Mucus turns over, and anything resting on it is cleared within minutes to a few hours, which sets a hard ceiling on how long a conventional mucoadhesive dosage form can act at an absorption site. Thiolated polymers, or thiomers, were designed to break that ceiling by carrying free sulfhydryl groups that form covalent disulphide bonds with the cysteine-rich subdomains of mucus glycoproteins rather than relying on the weak secondary interactions of first-generation mucoadhesives. This review traces the class from the 1999 report of cysteine-grafted polycarbophil to the preactivated and S-protected derivatives and thiolated cyclodextrins of the present decade. The covalent anchoring mechanism is examined against the direct evidence for it, chiefly the loss of adhesion when free cysteine competes for the polymer's thiols. Mucoadhesion gains reported across the literature span from roughly six-fold for thiolated hyaluronic acid to about 100-fold for chitosan-thiobutylamidine and close to 960-fold for a preactivated poly(acrylic acid) conjugate, though these numbers come from incompatible assays and are not directly comparable. Beyond adhesion, thiomers enhance permeation through glutathione-dependent inhibition of the protein tyrosine phosphatase that regulates tight junctions and of the P-glycoprotein efflux pump, and they prolong drug release by in situ disulphide crosslinking. In vivo work has shown oral absolute bioavailabilities near 20% for low-molecular-weight heparin and measurable systemic effect for salmon calcitonin and insulin in rodents. The one clear translational success is ocular: chitosan-N-acetylcysteine eye drops reached the market for dry eye disease and improved tear film thickness, break-up time and symptom scores in small clinical studies. Oral human evidence remains absent, which is the gap the field must now close.