Early weaning (EW) results in a transient period of impaired integrity of the intestinal mucosa that may be associated with reduced plasma concentration of glucagon-like peptide-(GLP) 2. We have previously shown that intragastric infusion of chenodeoxycholic acid (CDC) increases circulating GLP-2 in early-weaned piglets. The aim of this study was to expand previous work to establish whether feeding piglets a cereal-based diet supplemented with CDC can improve gut integrity and animal performance immediately after EW. A cohort of 36 piglets weaned at 20 days of age, 6.2 ± 0.34 kg of body weight (BW) were randomly assigned (n = 18) to receive a standard prestarter diet or the same diet supplemented with 60 mg of CDC per kg of initial BW for ad libitum intake until day 14 postweaning. Thereafter, all pigs were fed the same untreated starter diet for 21 days until the end of the study on day 35. On days 1, 7 and 14 blood samples were collected from 6 pigs per treatment to measure plasma GLP-2. On day 15, 6 pigs per treatment were euthanized to obtain intestinal tissue samples for later histological and gene expression analyses. Supplementing the diet with CDC tended to increase plasma GLP-2 (P < 0.07; 39 %) and the weight of the large intestine (P < 0.10; 11 %), and increased ileal crypt depth (P < 0.04; 15 %) after 14 days of treatment exposure. Although feed intake and BW gain were not affected by treatments, feeding CDC induced the expression of the cytokines TNF-α (P < 0.02; 1.9 fold), IL-6 (P < 0.01; 2.4 fold), and IL-10 (P < 0.006; 2.2 fold) and the tight junctional protein ZON-1 (P < 0.02; 1.5 fold) in the distal small intestine. This study showed that the oral administration of CDC to early-weaned pigs has the potential to improve the protection of the intestinal mucosa independently of relevant changes in gut growth.