Grape seed procyanidins (GSPs), widely known for their beneficial health properties, fail to bring about the expected improvement in piglets’ growth performance. The effects of dietary supplementation with GSPs on nutrient utilisation may be a critical influencing factor. Hence, the purpose of this study was to investigate the effects of dietary supplementation with GSPs on nutrient utilisation and gut function in weaned piglets. One hundred and twenty crossbred piglets were allocated randomly to four treatment groups, with three replicate pens per treatment and 10 piglets per pen. Each group was given one of the four dietary treatments: the basal diet (control group) or the basal diet with the addition of 50-, 100- or 150-mg/kg GSPs. The trial lasted 28 days. Faeces were collected from d 12 to 14 and from d 26 to 28 for measuring the coefficient of total tract apparent digestibility (CTTAD) of the nutrients. Blood samples were collected on d 14 and 28 for detecting the blood biochemical parameters. Two piglets per pen were slaughtered to collect the pancreas and intestinal digesta for evaluating the digestive enzyme activity and the coefficient of ileal apparent digestibility (CIAD) of the nutrients. On d 14 and 28, supplementation with 150-mg/kg GSPs significantly decreased the CTTAD of DM and CP in piglets. On d 14, GSPs supplementation at a concentration of 150 mg/kg led to a remarkable decrease in the CIAD of CP and gross energy (GE). On d 28, GSPs supplementation at a dose of 150 mg/kg generated a marked decline in the CIAD of DM, GE, CP and ether extract. Grape seed procyanidins supplementation at concentrations of 100 or 150 mg/kg inhibited the activities of lipase and amylase. In contrast, the jejunum mucosa maltase and sucrase activities increased due to the inclusion of GSPs at a concentration of 100 mg/kg in the piglet diet. Compared with the levels of the control group, the serum glucose and total protein levels were enhanced significantly by supplementation with GSPs at 100 mg/kg and reduced dramatically at 150 mg/kg. The serum diamine oxidase activity and endotoxin levels were decreased by GSPs supplementation in piglet diets. In conclusion, higher concentrations of GSPs in weaned piglet diets attenuated nutrient digestion and inhibited digestive enzyme activity; however, suitable concentrations of GSPs could promote brush-border enzyme activity, enhance serum glucose and total protein concentrations and decrease epithelial permeability.