The exploitation of easily accessible and nontoxic natural catechol compounds for surface functionalization and coating is attracting growing interest for biomedical applications. We report herein the deposition on different substrates of chemically stable thin films by autoxidation of 1 mM caffeic acid (CA) solutions at pH 9 in the presence of equimolar amounts of hexamethylenediamine (HMDA). UV-visible, mass spectrometric, and solid state 13C and 15N NMR analysis indicated covalent incorporation of the amine during CA polymerization to produce insoluble trioxybenzacridinium scaffolds decorated with carboxyl and amine functionalities. Similar coatings are obtained by replacing CA with 4-methylcatechol (MC) in the presence of HMDA. No significant film deposition was detected in the absence of HMDA nor by replacing it with shorter chain ethylenediamine, or with monoamines. The CA/HMDA-based films resisted oxidative and reductive treatments, displayed efficient Fe(II) and Cu(II) binding capacity and organic dyes adsorption, and provided an excellent cytocompatible platform for growing embryonic stem cells. These results pointed to HMDA as an efficient cross-linking mediator of film deposition from natural catechols for surface functionalization and coatings.