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This study was conducted to investigate the effects of Macleaya cordata extract (MCE) on growth performance, immune responses, antioxidant capacity, intestinal morphology and microbiota in weaned piglets. A total of 36 weaned piglets [Duroc× (Large White × Landrace)] with an average body weight of 6.55 ± 0.32 kg at weaning were used in a 21-day experiment. Pigs were divided into three treatments (n = 12). Control (basal diet); MCE (basal diet plus MCE) and ABO (basal diet plus 20 mg/kg falvomycin & 100 mg/kg aureomycin). Compared with the control group, piglets in the MCE and ABO groups had higher average daily gain, lower feed efficiency and diarrhea rates (P < 0.05). Serum IgG level in MCE -fed piglets was higher (P < 0.05) than that of control -fed piglets. A higher (P < 0.05) serum the activity of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) was observed in MCE-fed piglets than those in the control and ABO groups. The addition of MCE increased the amount of Lactobacillus spp. (P < 0.05), while decreased the amount of Salmonella spp. (P < 0.05) and tended to reduce the E. coli population (P < 0.10). Dietary MCE increased villus height and the villus height to crypt depth ratio in the duodenum, jejunum and ileum, and decreased the crypt depth in the jejunum of piglets (P < 0.05). In conclusion, dietary MCE supplementation would exert beneficial effects on growth performance, immune status, antioxidant capacity and the intestinal health and may be used as a potential alternative to antibiotics in weaned piglets.