Two hindered phenol antioxidants, HPAP-COOH and HPAP-HA for polyamide, were synthesized by bonding aromatic carboxylic acids and aromatic amides to hindered phenols. The antioxidant effect of the two antioxidants in PA6 was studied by thermal oxidative aging. The results showed that HPAP-COOH and HPAP-HA had good antioxidant effects, especially HPAP-COOH. PA6/HPAP-COOH exhibited excellent retention of tensile strength and bending strength after thermal oxidative aging, slightly higher than that of PA6/1098. The synthesized hindered phenol not only has a good antioxidant effect but also has a good plasticizing effect in PA6. The elongation at break of unaged PA6/HPAP-COOH and PA6/HPAP-HA was 3.7 and 8.3 times that of pure PA6, respectively. The good interaction between antioxidants and PA6 resulted in an excellent antimigration and plasticizing effect of antioxidants in PA6. The interaction mechanism between PA6 molecular chains and the two antioxidants was discussed. The interaction of HPAP-COOH and PA6 was enhanced by the reaction of the carboxylic acid groups and amino groups of PA6, as well as the intermolecular hydrogen. The interaction between HPAP-HA and PA6 was increased through intermolecular hydrogen bonds. HPAP-COOH and HPAP-HA inhibited the oxidation reaction and the cross-linking of the molecular chains in the interior of PA6. The service life of PA6 was greatly extended.