Turpiniae folium extract (TFE) has shown anti-inflammatory and immunomodulatory effects in broilers. However, its mechanisms remain unclear. The aim of this study is to investigate the underlying mechanisms by which TFE influences growth performance, jejunal morphology, immune function, antioxidant capacity and barrier integrity in broilers challenged with Lipopolysaccharide (LPS). A total of 240 one-day-old female broilers were randomly divided into four groups with six replicates of ten birds each. A 2 × 2 factorial design with TFE (basal diets supplemented with 0 or 500 mg/kg TFE) and LPS challenge (intraperitoneal injection of 1 mg/kg body weight of sterile saline or LPS at 21, 23 and 25 days of age). The trial lasted for 26 days. The results showed that: Prior to the LPS challenge, dietary supplementation with TFE for 21 days increased both average daily gain (ADG) (P = 0.037) and average daily feed intake (ADFI) (P = 0.045) in broilers. During the LPS challenge period, LPS challenge led to a decline in growth performance and a negative impact on intestinal morphology, while TFE supplementation significantly reversed these adverse effects, as evidenced by increases in ADG (P = 0.004), ADFI (P = 0.046), jejunal villus height (VH) (P = 0.035), the villus height to crypt depth ratio (VH/CD) (P = 0.007) and decreases in the feed-to-gain ratio (F/G) (P = 0.025), jejunal crypt depth (CD) (P = 0.049). LPS induced inflammatory responses and oxidative stress in the jejunum, leading to a significant upregulation of pro-inflammatory factor gene and protein expression, and a marked downregulation of anti-inflammatory and antioxidant gene and protein expression. TFE supplementation mitigated these effects by yielding completely opposite results except for the expression of toll-like receptor 4 (TLR4) protein (P = 0.916). LPS negatively regulates the expression of genes and proteins involved in intestinal mucosal barrier function. In contrast, TFE supplementation significantly upregulated the expression of zonula occludens-1 (ZO-1) (P <
0.001) gene and ZO-1 (P <
0.001), occludin (OCLN) (P <
0.001), claudin (CLDN) (P <
0.001) proteins. In conclusion, dietary supplementation with TFE effectively counteracts the intestinal immune and oxidative stress induced by LPS challenge in broilers, improves intestinal mucosal barrier integrity and tissue morphology, and ultimately mitigates the negative impact of LPS on broiler growth performance. This effect may involve the modulation of the Nrf2 and nuclear factor kappa B (NF-κB) signaling pathways.