This study aimed to develop amine-functionalized nanoparticles using supports of different chemical natures to protect hydrolyzed polyacrylamide (HPAM) polymers from thermochemical and mechanical degradation using static, dynamic, and molecular approaches. MgO (basic), Al 2 O 3 (neutral), and SiO 2 (acid) nanoparticles were functionalized with amine and characterized. To evaluate the performance of nanofluids based on HPAM, viscosity, mechanical assays, capillary numbers, oil recovery curves, and injectivity tests were made. To obtain insights into the interactions between HPAM and the nanoparticles, molecular dynamics (MD) was completed. The results demonstrated a relationship between the HPAM protection, the chemical nature, and the concentration of the nanoparticles used, showing a preference for neutral nanostructures such as Al 2 O 3 /amine at 10 mg L −1 , which improved up to 77, 920, 34, and 15.5% the viscosity, capillary number, mechanical stability, and oil recovery of HPAM, respectively. HPAM viscosity was 3 times higher and up to 41 times higher using nanoparticles of Al 2 O 3 /amine. MD allowed us to understand the ability of Al 2 O 3 /amine to extend the HPAM chains and improve the radius of gyration, up to 26%, through the interaction by hydrogen bonds and their ability to trap cations (up to 33%), preventing them from interacting with the acrylic groups of the HPAM molecules and the folding of the polymer. This proposal is based on multidisciplinary studies to understand nanotechnology applied to enhanced oil recovery (EOR) processes.