Palygorskite (Pal), a silicate clay mineral abundant in the natural world, has been recently receiving increased attention in animal production. The aim of the present study was to evaluate the effects of Pal supplementation on growth performance, organ weight, inflammatory response, intestinal barrier function, and antioxidant capacity of broilers challenged with lipopolysaccharide (LPS) at an early age. In total, 144 1-day-old male broiler chicks were allocated to one of three treatment groups consisting of six replicates of eight chicks each. The three treatments were: 1) non-challenged broilers fed basal diet (control group); 2) LPS-challenged broilers fed basal diet; 3) LPS-challenged broilers fed basal diet supplemented with 10 g/kg Pal. Broilers were injected intraperitoneally with LPS at a dosage of 1 mg/kg body weight or an equivalent amount of saline (control group) at 17, 19, and 21 days of age. LPS challenge resulted in inferior growth performance to that of the control group (body weight at 21 days of age, 721 g vs 657 g; gain-to-feed ratio, 0.68 vs 0.59), and higher relative weights of liver and spleen in broilers (P < 0.05). Pal supplementation did not improve growth performance (body weight at 21 days of age, 657 g vs 660 g; gain-to-feed ratio, 0.59 vs 0.61) or decrease the relative organ weight of LPS-challenged broilers (P> 0.05). Furthermore, LPS treatment increased interleukin-1β concentration in serum and ileal mucosa, and interferon-γ concentration in jejunal mucosa (P < 0.05). In contrast, the concentrations of interleukin-1β in serum and interferon-γ in jejunal mucosa in LPS-challenged broilers were reduced by Pal supplementation (P < 0.05). LPS challenge increased the abundance of interferon-γ and claudin-3 mRNA in jejunal mucosa, but reduced zonula occludens-1 mRNA expression in ileal mucosa (P < 0.05). These changes in mRNA abundance of the aforementioned genes in LPS-challenged broilers were normalized on Pal supplementation (P < 0.05). LPS injection increased serum d-lactic acid concentration in broilers (P < 0.05), and this increase was reversed by Pal supplementation (P < 0.05). LPS challenge also increased malondialdehyde accumulation in serum and jejunal mucosa, but reduced glutathione concentration in jejunal and ileal mucosa of broilers (P < 0.05). In contrast, dietary Pal supplementation decreased malondialdehyde accumulation, but increased glutathione concentration in jejunal mucosa of LPS-challenged broilers (P < 0.05). It can, therefore, be concluded that Pal can be added to diets of LPS-challenged young broiler chickens to reduce inflammation and improve antioxidant capacity.