Oxidative stress is currently considered to be the main cause of brain aging. Astaxanthin can improve oxidative stress under multiple pathological conditions. It is therefore hypothesized that astaxanthin might have therapeutic effects on brain aging. To validate this hypothesis and investigate the underlying mechanisms, a mouse model of brain aging was established by injecting amyloid beta (Aβ)25–35 (5 μM, 3 μL/injection, six injections given every other day) into the right lateral ventricle. After 3 days of Aβ25–35 injections, the mouse models were intragastrically administered astaxanthin (0.1 mL/d, 10 mg/kg) for 30 successive days. Astaxanthin greatly reduced the latency to find the platform in the Morris water maze, increased the number of crossings of the target platform, and increased the expression of brain-derived neurotrophic factor, synaptophysin, sirtuin 1, and peroxisome proliferator-activated receptor-γ coactivator 1α. Intraperitoneal injection of the sirtuin 1 inhibitor nicotinamide (500 μM/d) for 7 successive days after astaxanthin intervention inhibited these phenomena. These findings suggest that astaxanthin can regulate the expression of synaptic proteins in mouse hippocampus through the sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α signaling pathway, which leads to improvements in the learning, cognitive, and memory abilities of mice. The study was approved by the Animal Ethics Committee, China Medical University, China (approval No. CMU2019294) on January 15, 2019.