Cadmium (Cd) is a toxic heavy metal pollutant widely present in the environment. It can accumulate in organisms through the food chain and pose a serious health threat to various organisms, including poultry. The liver is one of the main target organs for cadmium toxicity. This study aimed to explore the mechanism of cadmium exposure causing liver damage, and to explore the potential protective effects of Astilbin (ASB) and Taxifolin (TAX). Therefore, in vivo experiments with 60 one-day-old Hy-line brown male chickens were evenly divided into six groups: the CON, ASB, TAX, Cd + ASB, Cd + TAX, and Cd groups. On the 90th day, the Cd and metallothionein contents were detected in the chicken liver, and H&E and TEM were used to visualize pathological changes and ultrastructural damage of the liver tissue. Key indicators of oxidative stress, including the Nrf2 antioxidant system and apoptosis in chicken liver tissues, were also investigated. Tetramethylated Astilbin (TMA) was obtained by methylating the phenolic hydroxyl group of ASB and LMH cells, and was treated with ASB, TAX, TMA, and ML385 (a Nrf2 inhibitor). Results showed that ASB and TAX activated the expression of the Nrf2/HO-1 signaling pathway, promoted Nrf2 expression and nuclear translocation in chicken liver, and increased the activities of downstream antioxidant enzymes such as Glutathione (GSH), superoxide dismutase (SOD), and Total antioxidant capacity (T-AOC) by promoting Nrf2 translocation into the nucleus. It alleviated the increased expression of pro-apoptotic factors and the decreased expression of anti-apoptotic factors induced by Cd in the liver. This study shows that ASB and Tax can protect chicken livers from damage caused by early-life cadmium exposure.