This study explored the impact of fresh sweet potato vine on the growth as well as the metabolites and colon microbial composition in Chinese Meishan gilt. Twenty Meishan gilts (body weight 30 ± 0.18 kg, n = 10 per treatment) were randomly assigned to a control (CON) or sweet potato vine (SPV) supplementation diet treatment. Gilts were housed in individual stalls. In the SPV treatment, 2 kg fresh sweet potato vine was used instead of 0.18 kg basal diet which provided the same amount of digestive energy and crude protein with the exception of crude fiber (CON, 51.00 g/d vs. SPV, 73.94 g/d) in terms of dry matter intake. Gilts were slaughtered and samples were collected on day 19 after the third estrus cycle. The SPV treatment tended to increase slaughter weight of gilts (p = 0.07); it also increased (p < 0.05) gastrointestinal tract weight and intestinal muscle layer thickness. SPV treatment also decreased (p < 0.05) carcass yield and subcutaneous adipose tissue. The concentration of zonulin and endotoxin in plasma was decreased (p < 0.05) as the gilt consumed the SPV diet. Colonic fecal concentrations of endotoxin, lipocalin-2, and tumor necrosis factor-α (TNF-α) were decreased (p < 0.05), and interleukin-10 (IL-10) was increased (p < 0.05) in the SPV treatment. Butyric acid and acetate concentration in colonic content as well as acetate concentration in caecal content were increased (p < 0.05) in the SPV treatment. Furthermore, the expression of carnitine palmityl transferase (CPT-1) and peroxisome proliferator-activated receptor-α (PPAR-α) in gilt liver in SPV treatment was increased (p < 0.05) in comparison with CON treatment. Meanwhile, the composition of the colon microbes was also altered by SPV; representative changes included an increase in Lactobacillus, Bacteroides, Roseburia, and Lachnospira. These results indicate that gilt fed with sweet potato vine had decreased gut permeability, endotoxin and pro-inflammatory cytokines concentrations; colonic fecal microbiota was also changed, which may be further beneficial to the intestinal health of Chinese Meishan gilt.