Mice were administered subcutaneous injection of D-galactose to produce an animal model of aging, which was used to study the in vivo effect of fermented plant extract (FPE) on antioxidant activity. Parameters including the activity of three characteristic antioxidant enzymes, namely superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) as well as the malondialdehyde (MDA) content in the serum and liver of mice of both sexes were extensively evaluated. Meanwhile, spleen index and thymus index were used as the indicators for the preliminary assessment of the impact of FPE on mice immunity in vivo. The results showed that compared with the model group, the activities of SOD, CAT, and GSH-Px in serum and liver of mice (both sexes) were significantly enhanced and corresponding MDA content was decreased in the group that received 1.5 mL/kg FPE gavage. Additionally, spleen and thymus indices of mice were increased to some extent in groups that received 0.24 and 0.6 mL/kg FPE gavage. Thus, FPE enhanced antioxidant activities in vivo, implying an anti-aging effect and may have potential to strengthen the immune system.