Metabolic abnormalities in rats fed a high-sucrose diet (HSD)—a well-established model of Metabolic Syndrome (MetS)—are accompanied by cortical alterations and cognitive decline. This model is valuable for studying potential neuroprotective interventions in MetS-related brain disorders (MSRBD). In this study, we evaluated the neuroprotective effects of astaxanthin (ASTX) -a powerful antioxidant- derived from freshwater crustaceans in a rodent model of MetS. Male Wistar rats were fed for 90 days with either a standard commercial rodent diet, a HSD, or a HSD supplemented with an ASTX-rich extract (10 mg/kg body weight/day, administered orally). We conducted the novel object recognition test (NORT) and T-maze memory tasks. Additionally, in the cerebral cortex, we measured: (a) proteins involved in energy metabolism and the insulin signaling pathway; (b) myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and chlorotyrosine (Cl-Tyr)- and nitrotyrosine (NT)-modified proteins; and (c) acetylcholinesterase (AChE) activity. Compared with HSD-fed rats, HSD+ASTX-fed rats showed (a) improved cognitive performance in both memory tasks; and (b) in the cerebral cortex, increased levels of GLUT-3, hexokinase, total AMPK, and pThr172AMPK levels, along with reductions in MPO, Cl-Tyr, and AChE activity. Levels of pAKT, iNOS, and NT were elevated in both groups. Our results suggest that ASTX could be a potential strategy for preventing or attenuating MSRBD.