To research the influence on serum metabolism caused by Macleaya cordat extract and antibiotics in weaning goats (Capra hircas). Goats with similar body condition and consistent genetic background were randomly divided into three treatments. There were the control group (CON group) fed ordinary diet, Macleaya group (MAC group) fed control diet supplemented with 0.3 g/d Macleaya cordata extract and the antibiotics group (ANT group) fed control diet supplemented with 21 mg/(kg·d–1) vancomycin and 42 mg/(kg·d–1) neomycin. The results of determination showed that supplementing Macleaya cordata extract or antibiotics did not affect the growth performance (P>0.05). However, compared with the CON group, supplemental Macleaya cordata increased the level of interleukin-10 (IL-10) in the serum (P<0.01). In addition, when compared with the CON group the content of α- ketoglutarate in antibiotics group and MAC group decreased. Antibiotics increased the contents of tryptophan, phenylalanine, chenodeoxycholic, and the content of taurodeoxycholic acid decreased. The contents of glutamic acid and leucine decreased, while the contents of guanosine and inosine increased by Macleaya cordata supplementation. KEGG analysis showed that the differential metabolites of MAC group and ANT group partially coincide in the pathways of amino acid metabolism and synthesis. Compared to CON group, antibiotics treatment affected arachidonic acid metabolism, unsaturated fatty acid biosynthesis and butyric acid metabolism, etc. However, the differential metabolites of MAC group were significantly enriched in amino acid metabolism, glutathione metabolism and purine metabolism pathway compared with the CON group. In conclusion, the addition of antibiotics or Macleaya cordata in the diet can change the amino acid metabolism in the serum, while the addition of Macleaya cordata can enhance the immune function of the body, and can replace antibiotics in the application of feed additives.