We developed a facile synthesis for a series of multifunctionalized polyesters by Passerini three-component polymerization (Passerini-3CP) in a "one-pot" method at room temperature using serial dicarboxylic acids, dialdehyde, and tert-butyl isocyanide as monomers. First, the effects of monomer feed ratio, monomer concentration, and different dicarboxylic acids involved in the polymerization were systematically investigated. The in situ FTIR and GPC measurements have suggested a step-growth mechanism for Passerini-3CP. Second, five succinic acid end-capped polyethylene glycols (S-PEGs) with different molecular weights of 400, 800, 1000, 2000, and 4000 g/mol were prepared and selected as dicarboxylic acids for the subsequent Passerini-3CP to fabricate the thermosensitive and biocompatible polyesters. Among the five resulting polyesters, four polyesters from S-PEG-400, S-PEG-800, S-PEG-1000, and S-PEG-2000 show reversible response to the external temperature, and the lower critical solution temperature (LCST) in water is in the range of 28.5-84.2 °C. Through the copolymerization of S-PEG-400 and S-PEG-800, the LCSTs for functional polyesters can be conveniently controlled to be 38.7, 42.3, and 58.0 °C, respectively. After 24-72 h of incubation in polyester solution, the viability rate of HeLa cells reached up to 80-107%, showing its excellent biocompatibility. The cleavable polyesters were also prepared by integrating S-S bonds onto their backbones in Passerini-3CP of 3,3'-dithiodipropionic acid as one comonomer for the biomedical applications. With the aid of the hydrophobicity of doxorubicin (DOX) and thermosensitivity of polyesters, the doxorubicin-loaded carriers with the size of 200-400 nm and core-shell structure were easily obtained by dialysis below LCST and subsequent heating to LCST. The effective release of DOX from the carriers can be triggered by the characteristic reaction of l-glutathione (GSH) with S-S bonds in the functionalized polyester backbones.