A 21-day study was conducted to determine whether isoleucine might limit the performance of piglets fed low-crude protein (CP), amino acid (AA)-supplemented diets and to investigate the potential benefits of low-CP diets on gastrointestinal health in weaned pigs. Ninety-six piglets (initial BW = 6.44 ± 0.14 kg), housed four per pen, were randomly assigned to one of four diets, resulting in six replicate pens per diet. Dietary treatments were as follows: (1) 210 g/kg CP diet, (2) 190 g/kg CP diet deficient in isoleucine, (3) 190 g/kg CP diet supplemented with crystalline isoleucine up to the level in the 210 g/kg CP diet and (4) 170 g/kg CP diet supplemented with isoleucine and valine on the ideal protein ratio basis (60% and 70% relative to lysine, respectively). Pigs were allowed to adapt to the new environment for 4 days before the experiment commenced. Overall, pigs fed the 210 g/kg CP diet had higher (P < 0.05) average daily gain and lower (P < 0.05) feed : gain ratio compared with those fed the other diets. The faecal consistency score of pigs fed the 210 g/kg CP diet was higher (P < 0.05) than those fed the other diets. Pigs fed the 170 g/kg diet had lower (P=0.02) small intestine weight than those fed the 210 g/kg CP diet. Pigs fed the 210 g/kg CP diet had deeper (P < 0.05) crypt in the duodenum and ileum and higher (P < 0.05) ammonia N concentration in caecal digesta than those fed the other diets. There were no effects of diet on microbial population and volatile fatty acid concentration in the caecal digesta except for propionic acid whose concentration was higher (P < 0.05) for pigs fed the 170 g/kg diet than those fed the 190+isoleucine and the 210 g/kg CP diets. The results indicate that the low-CP, AA-supplemented diet reduced crypt hypertrophy, ammonia N concentration in the caecal digesta, small intestine weight and the performance of piglets. Also, the results of the current study were inconclusive with respect to whether isoleucine may limit the performance of pigs fed a low-CP, AA-supplemented diet.