Abstract Increased proteolytic fermentation may lead to negative effects on gastrointestinal health and function, which ultimately impact on performance. The objective was to develop and validate, by investigating performance and gut structure outcomes, an index of indigestible protein content (IDP) in weaned pigs. Ninety-four studies reporting growth performance [average daily gain (ADG), average daily feed intake (ADFI), gain: feed (GF), initial (IBW) and final body weight (FBW)] and duodenal histomorphometries [villus height (VH), crypt depth([CD), and villus height: crypt depth ratio (VCR)] variables of pigs fed different protein content (CP) and sources in the diet were included. Diets were recalculated using a common database to generate the IDP from each study. Studies were grouped by similarity in performance in two clusters (C1 and C2) by hierarchical clustering on principal components (HCPC). The effects of cluster were investigated. Quadratic response plateau (QRP) models were fitted to assess the interrelationships between ADG, ADFI, GF, VH, CD, and VCR with the dietary CP or calculated IDP content within cluster. Pigs from C2 had greater IBW (6.3 vs. 8.8 ± 0.2kg), FBW (10.2 vs. 17.2 ± 0.7kg), ADG (0.2 vs. 0.4 ± 0.0kg/d), and ADFI (0.3 vs. 0.6 ± 0.1kg/d) compared with C1 (P < 0.05). There was no effect of cluster (P > 0.05) on VH (405.5 vs. 405.5 ± 15.8μm), CD (232.5 vs. 220.7 ± 10.1μm), or VCR (1.9 vs. 2.0 ± 0.3μm). Pigs from C1 achieved break point (BP) and plateau (Pl) for VH (BP = 24.25%, Pl = 96.32μm; P < 0.05) when fed increasing CP content and for ADG (BP = 2.32%, Pl = 0.28kg/d; P < 0.05) and GF (BP = 2.18%, Pl = 0.83kg/kg; P < 0.05) when fed increasing calculated IDP content. Pigs from C2 fed increasing content of calculated IDP achieved BP and Pl for ADG (BP = 3.04%, Pl = 0.54kg/d; P < 0.05). Our findings suggest that calculated IDP might be a reliable index to investigate the effects of proteolytic fermentation on pig performance, particularly in the immediate post-weaning phase.