Catalyst-free thermal polyesterification has recently emerged as a potential strategy for designing biodegradable thermoset polymers, particularly polyol-based polyesters for biomedical applications. These thermoset polyesters are synthesized through polycondensation of polyol and polyacid without the presence of catalyst or solvents. The mechanical properties, degradation rates, crystallinity, hydrophilicity, and biocompatibility can be controlled by adjusting the monomer feed ratios and curing conditions. These polyesters often degrade via surface erosion that allows the polymers to maintain structural integrity throughout hydrolysis. Additionally, polyol-based polyesters demonstrated good biocompatibility as non-toxic catalysts and/or solvents involved in the reaction, and the monomers used are endogenous to human metabolism which can be resorbed and metabolized in various physiological pathways. This review summarizes the polyol-based biodegradable polyesters that were synthesized by catalyst-free polyesterification.