Weaning transition is often associated with the occurrence of the post-weaning diarrhoea syndrome (PWDS). The reduction of dietary crude protein (CP) has been intensively used as a strategy for controlling PWDS. The aim of the present meta-analysis was to report the effect of the reduction of dietary CP on the intestinal parameters related to the gut health, growth and diarrhoea of post-weaning piglets. A literature review of the articles published from 2006 to 2019 produced 48 articles and, of these 26 were selected. Parameters (bacterial metabolites, pH, microbiota diversity, intestinal morphology, inflammation markers, growth, faecal score) were extracted, expressed as a percentage of the control diet and analysed using a general linear model which included the study, reduction in points of dietary CP, and the ratio of digestible Lysine and dietary CP (dLys/CP) as factors. The reduction of dietary CP decreased ammonia (p < .0001), pH (p = .039), total short-chain fatty acids (SCFAs) (p = .027), biogenic amines including cadaverine (p = .034) and putrescine (p = .030) and the expression of TLR4 (p < .0001) in the intestine and also reduced the faecal score (p = .002). The dLys/CP ratio increased the level of Lactobacilli and the expression of TLR4 (p < .05), and tended to increase acetic acid (p < .1). Crypt depth, villus height, microbiota diversity and growth remained unchanged. In conclusion, this study confirmed that a reduction of dietary CP could reduce bacterial protein fermentation and the production of potentially toxic metabolites. In turn, this could result in lower intestinal inflammation and a decreased risk of diarrhoea in weaning piglets. Highlights Reducing the dietary crude protein can decrease the fermentation of undigested dietary protein, especially in the large intestine. Lowering undigested dietary protein results in a reduction of the intestinal pH and potentially toxic metabolites, including ammonia and amines. Diets with lower crude protein reduce inflammation of the intestinal mucosa and the post-weaning diarrhoea of piglets without compromising performance.