<p>This study investigated the effects of osteopontin (OPN) combined with milk fat globule membrane (MFGM) proteins on scopolamine-induced learning and memory impairment in mice. A dementia model was established through intraperitoneal injection of scopolamine, followed by random allocation into seven experimental groups: blank control, model control, OPN alone, MFGM alone, and three combination groups (low-, intermediate-, and high-dosage OPN + MFGM). Cognitive performance was evaluated using the Morris water maze test, accompanied by quantification of hippocampal acetylcholinesterase (AChE) activity, antioxidant enzyme activities (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px]), malondialdehyde (MDA)) from both hippocampal tissue and serum. We found significant cognitive improvements in the intermediate- and high-dosage combination group to the model group, which had reduced escape latency, increased platform crossings, and prolonged target quadrant duration in the water maze test. Biochemical results suggest that these combination treatments significantly suppressed AChE activity in hippocampal tissue while they enhanced antioxidant capacity through elevated SOD and GSH-Px activities, accompanied by reduced MDA levels in both brain and serum. Our study demonstrates that the combination of OPN and MFGM administration improved learning and memory in mice with scopolamine-induced dementia through dose-dependent effects on the central cholinergic nervous and antioxidant system.</p>