This study aimed to investigate the effects of dietary supplementation with Macleaya cordata extract (MCE) containing protopine and allotypotopine on the growth performance and liver health in broiler chickens. A total of 486 1-day-old male AA broiler chickens were randomly assigned to the following three groups: (1) control (CON) group, broiler chickens fed a basal diet; (2) AGP group (positive control), broiler chickens fed a basal diet supplemented with 50 mg/kg aureomycin; (3) MCE group, broiler chickens fed a basal diet supplemented with 0.6 mg/kg MCE including 0.4 mg/kg protopine and 0.2 mg/kg allotypotopine. The results showed that the MCE group had significantly higher final body weight and average daily gain from d 0 to 42 than the other groups (p < 0.05), and groups MCE and AGP both had significantly lower feed-to-gain ratio from d 0 to 42 than the CON group (p < 0.05). Serum total protein, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, glucose, immunoglobulin A, immunoglobulin M, and complements (C3, C4) concentrations in the MCE group were significantly higher than in the CON group (p < 0.05). Dietary MCE or aureomycin supplementation significantly reduced the hepatic contents of 8-hydroxy-2'-deoxyguanosine, malondialdehyde, interleukin (IL)-1β, IL-6, NLRs family pyrin domain containing 3 (NLRP3), and caspase-1 in the liver (p < 0.05). Moreover, MCE or aureomycin supplementation significantly inhibited mRNA expressions of Toll-like receptor 4, myeloid differentiation factor 88, nuclear factor-κB, and NLRP3, as well as the expression ratio of Bax to Bcl-2 mRNA (p < 0.05). Therefore, our study suggested that dietary supplementation with 0.6 mg/kg MCE containing protopine and allocryptopine improved growth performance and benefited liver health in broiler chickens possibly through inhibiting caspase-1-induced pyroptosis by inactivating TLR4/MyD88/NF-κB/NLRP3 signaling pathway, and provided support for the application of MCE containing protopine and allocryptopine as an alternative to antibiotics in the feed industry.