We investigated the time-course effects of therapeutic antibiotics on intestinal microbial composition and metabolism in an ileal-cannulated pig model. Sixteen ileal-cannulated piglets (12 ± 0.5 kg) were assigned to two groups (n = 8) and fed standard diets with or without antibiotics. At 4 days before, and at days 2, 7, and 13 after antibiotic administration, ileal and fecal samples were collected for analysis of microbiota composition via 16S rRNA MiSeq sequencing and metabolites (short-chain fatty acids, biogenic amines, and indole). It was found that Lactobacillus and Bifidobacterium had decreased by an average 2.68-fold and 508-fold in ileum on days 2-13, and by an average 45.08-fold and 71.50-fold in feces on days 7-13 (P < 0.05). Escherichia/Shigella had increased by an average 265-fold in ileum on days 2-13, and by an average 36.70-fold in feces on days 7-13 (P < 0.05). Acetate concentration had decreased in ileum by an average 2.88-fold on days 2-13, and by 1.83-fold in feces on day 7 (P < 0.05). Cadaverine concentration had increased by an average 7.03-fold in ileum on days 2-13, and by an average 9.96-fold in feces on days 7-13 (P < 0.05), and fecal indole concentration had increased by an average 2.51-fold on days 7-13 (P < 0.05). Correlation analysis between significant microbes and metabolites indicated that the antibiotic-induced microbiota shift appeared to result in the changes of intestinal metabolism. In conclusion, antibiotic administration led to dynamic changes in microbial communities and metabolism in ileum and feces, with ileal microbiota being more prone to shift than fecal microbiota.