Responsive polymers have significant importance and promising applications in the field of biomedicine. In this study, benzimidazole (BI)-based polyesters were synthesized for the first time via amine-ene click polycondensation. Benzimidazolethione (BITO) and aliphatic diacrylates (DA) were selected as clickable monomers using the organic catalyst 4-dimethylaminopyridine (DMAP) to obtain benzimidazole-based polyesters. 1,4-Butylene diacrylate (BDA) and poly(ethylene glycol) diacrylate (PEGDA) were used as model DA to synthesize lipophilic and hydrophilic polymers, respectively. Furthermore, click polymerization of BITO with BDA and PEGDA was conducted for tricomponent polycondensation. ¹H NMR, FTIR and GPC spectra demonstrated that the BITO-based polyesters were successfully synthesized via the click condensation of amine-ene. The obtained polymers exhibited pH, reactive oxygen species (ROS) and β-cyclodextrin (β-CD) triple responsiveness and the amphiphilic BITO polyester can self-assemble into nanoparticles. We believe that these novel BITO polyesters have great potential as drug delivery systems for controlled drug release in nanomedicine.