Hyperbranched polymers have been widely used in different applications. In this work, the A(2) + B-3 polymerization procedure was utilized to synthesize highly branched polyamide-imide compounds. Response surface methodology (RSM) was applied for the optimization of the reaction yield and polymer properties. Monomers used revealed the highest yield when appended to a specified quantity of a series of catalysts at optimized dimethyl sulfoxide solvent loading of 1 wt%. The resulting highly branched optically active polymer with completely water solubility was used in the preparation of nanocomposites based on graphene oxide (GO) and functionalized graphene oxide (FGO) nanoplates. The impact of FGO on the catalytic activity of the polymers was measured in terms of D,L-phenylglycine methyl ester hydrolysis in water. The optimized FGO content was 30 wt %, responsible for a very high enantioselectivity of 97.3% and chemical activity. Various analyses including Fourier transform infrared spectroscopy, wide-angle X-ray diffraction, differential scanning calorimetry, elemental analysis, and H-1-NMR, were conducted to uncover structural and morphological characteristics of the obtained polymers. Exceptionally, the enantioselectivity of the obtained catalysts was improved after functionalization, as a result of FGO localization in the microstructure.