To explore the protective effect of resveratrol on oxidative casein- induced learning impairments in mice and the possible underlying mechanism, thirty-six 7-week-old Kunming male mice were randomly divided into four groups: the blank control group (CT), oxidized casein group (CO), resveratrol low-dose group (LR), and resveratrol high-dose group (HR). The experimental results showed that after the resveratrol intervention, the learning and memory abilities of mice were improved, the latency of finding the platforms was shortened by 20.85% and 9.63%, respectively, for the low-dose group (LR) and the high-dose group (HR), the number of crossing the platforms increased by 53.63% and 47.57%, respectively, and the percentage of residence time in the target quadrant (where the platform was located) out of the total time increased by 103.69% and 53.68%, respectively. In addition, the body’s antioxidant capacity increased, the level of total antioxidant capacity (T-AOC) and the activities of antioxidant enzymes (SOD and CAT) significantly increased (P<0.01), whilst the content of malondialdehyde (MDA) decreased (P<0.05). The morphology of hippocampus and amygdala nerve cells were regular, the inflammatory aggregation state was ameliorated, the expressions of inflammation-related genes (IL-1β, IL-6, and TNF-α) were significantly down-regulated (P<0.05), and the expressions of learning and memory related genes (BDNF, TrkB, and CREB) were significantly up-regulated (P<0.01). In conclusion, resveratrol could effectively ameliorate the oxidized casein-induced learning and memory impairments in mice, and the underlying mechanism may be related to the activation of the BDNF/TrkB/CREB signaling pathway to improve the antioxidant and anti-inflammatory capabilities of the body.