Computer-aided molecular design (CAMD) is a well-known tool for the theoretical assessment of chemical structures before their experimental synthesis. In this study, we used this method to consider the important criteria for a chemical structure as an energetic plasticizer for an energetic azido binder. The number of new azido-ester structures were initially designed, and their physicochemical and energetic properties were determined via theoretical calculation by molecular dynamics simulations and machine learning-based methods. Considering the balances between several criteria, two of these theoretical chemical structures (including GTAA (glyceryl tris(azidoacetate)) and TEGBAA (triethyleneglycol bis(azidoacetate))) were then selected, synthesized, and characterized. The comparison of experimental and theoretical results to evaluate the physicochemical properties of these new azido-ester plasticizers showed an acceptable agreement between the two methods. Finally, the compatibility and efficiency of these two new azido-ester plasticizers on the rheological and thermal properties of glycidyl azide polymer (GAP) were investigated using rheometry and DSC analyses, and compared with some common energetic plasticizers. The results confirmed that these two new azido-esters are appropriate plasticizers for GAP since they exhibited higher safety over comparable plasticizers, in addition to the real performance.