Weaned pigs are highly susceptible to gut infections, underscoring the need to develop feeding strategies to manage gut health. A study was conducted to determine the effects of lipid-coated sodium butyrate (NaB) and enzymatically hydrolyzed yeast cell wall product (EYP) on growth performance and indicators of intestinal structure and function in nursery pigs. A total of 96 weaned pigs (initial BW = 6.60 ± 0.88 kg) housed in 24 pens (four pigs/pen) were fed three diets in a randomized complete block design. The diets were corn-soybean meal-based without (CON) or with 0.05% NaB or 0.1% EYP. Growth performance and fecal score were determined by the feeding phase. During days 10-13, one pig from each pen was euthanized for measuring organ weights, blood immune response, histology and permeability of small intestine, electrophysiological parameters of jejunum mounted in Ussing chambers, and gut microbiome. Dietary NaB, but not EYP, increased (P <
0.05) overall gain-to-feed ratio by 16%. In comparison to CON, dietary EYP increased (P <
0.05) the cecum weight by 36%, and dietary NaB or EYP tended to increase (P <
0.10) the villous height to crypt depth ratio in duodenum by 12%. Dietary NaB or EYP had no influence on the serum concentrations of immunoglobulins A, G, M, and tumor-necrosis factor-α. Dietary NaB decreased (P <
0.05) the jejunal flux of fluorescein isothiocyanate-dextran flux by 32%, whereas dietary EYP tended to reduce (P = 0.10) it by 21% compared to CON. Also, dietary Nab and EYP decreased (P <
0.05) jejunal short circuit current by 52 and 50%, respectively, compared to CON. Dietary EYP increased (P <
0.05) the relative abundance of Sporobacter and Desulfovibrio genera in the cecum. Dietary EYP increased (P <
0.05) the relative abundance of Verrucomicrobia phylum and Odoribacter, Enterococcus, and YRC22 genera in feces. In conclusion, dietary NaB improved feed efficiency and reduced jejunal permeability to fluorescein isothiocyanate-dextran 4 kDa, implying that it improved intestinal integrity in nursery pigs. Thus, NaB product fed in the current study can be included in diets for weaned pigs to improve their performance through improved gut integrity. Dietary EYP increased cecum weight, implying that dietary EYP improved cecal fermentation capacity. It also modified cecal and fecal microbial composition. Thus, the EYP product fed in the current study can be added in diets for weaned pigs to improve the fermentation of feed in the hindgut.