The lemon flavonoid extract Eriomin (LE), which is rich in eriocitrin, has demonstrated antioxidant and anti-inflammatory properties in both animal and human studies. Given the established interplay among aging, oxidative stress, and inflammation, this study investigated the influences of LE on the pituitary-adrenal (PA) axis in aged rats and its potential to mitigate age-related physiological changes in this system. The effects of LE (40 mg/kg/day suspended in sunflower oil) on the morphofunctional properties of the PA axis were studied in 24-month-old male Wistar rats following four weeks of oral treatment. Control groups included vehicle-treated (sunflower oil; CON) and untreated intact controls (ICON). Stereological and imaging analyses revealed no significant changes in pituitary ACTH cells; however, gene expression was significantly downregulated in the LE group compared to both controls ( ≤ 0.05). LE treatment resulted in a significant reduction in adrenal gland weight ( ≤ 0.05), adrenal gland volume ( ≤ 0.01), zona fasciculata (ZF) volume ( ≤ 0.01) and ZF cell volume ( ≤ 0.05). These changes were accompanied by a significant decrease in serum corticosterone levels ( ≤ 0.05). In conclusion, LE downregulated PA axis activity in aged rats. Considering the association between age-related increases in PA activity and adverse health outcomes, citrus flavonoid extracts such as LE may hold promise as anti-aging supplements aimed at mitigating age-related stress dysregulation.