In order to investigate the anti-aging performance of nano-modified natural ester insulating oils, in this paper, two different types of nanoparticles are selected to modify insulating oils. We studied the microscopic mechanism of nano-modified models using molecular simulation techniques. Three models were established: an oil–water model without the addition of nanoparticles and two which contained nano-Fe3O4 and nano-Al2O3 particles, where the concentration of water was 1 wt.%. The research found that the diffusion of water molecules in the nano-modified model was slow, and the water molecules generated from transformer insulation aging were adsorbed around the nanoparticles, which inhibited the diffusion of water molecules, reduced the hydrolysis of ester molecules, and effectively enhanced the anti-aging performance of natural ester insulating oil. Compared with two different types of nano-modified models, the interface compatibility between nano-Fe3O4 and natural ester insulating oil is better, the composite model is stable, the change rate of the diffusion coefficient with temperature is small, there are more hydrogen bonds generated by nano-Fe3O4 and water molecules, and the anti-aging performance of the nano-Fe3O4-modified oil model is better.