ABSTRACT Shrimp oil is rich in polyunsaturated fatty acids and astaxanthin, which possesses high antioxidant activity. This study aimed to investigate the impact of shrimp oil on protection of brain damage and improvement of neurological outcomes after chronic cerebral hypoperfusion (CCH). Male Wistar rats were subjected to occlusion of the bilateral common carotid arteries and were divided into six groups: sham‐operated, 2‐vessel occlusion (2VO), 2VO‐treated with shrimp oil at the dose of 130, 260, and 520 mg/mL, and 2VO‐treated with resveratrol. Shrimp oil or resveratrol was administered via oral gavage after surgery once a day for 4 weeks. Shrimp oil reduced the level of cerebral damage after CCH associated with lower oxidative stress as indicated by attenuation of the levels of malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), and 4‐hydroxynonenal (4‐HNE). The shrimp oil treatment also initiated the antioxidant‐mediated nuclear factor E2‐related factor 2 (Nrf2)/heme‐oxygenase (HO‐1) pathway, reduced the hyperphosphorylation of tau, reduced neuronal cell death, promoted synaptic plasticity, and consequently promoted cognitive function. Shrimp oil exhibited neuroprotective effects against CCH‐induced cognitive impairment, which could be partially mediated through regulation of oxidative stress and neuronal apoptosis.