Fiber-rich (HF) diets are typically supplemented with enzymes to improve their nutritive value and to offset their negative effects on pig growth. However, studies on enzyme effect in pigs have yielded inconsistent results on nutrient digestibility and growth. Although the inconsistencies observed could be explained by differences in substrate and experimental conditions and enzyme characteristics among studies, how enzymes influence metabolic and physiological responses in pigs is still not clear. Therefore, three experiments were conducted, using 3 dietary treatments (control, HF and HF diet supplemented with enzymes), to elucidate the effects of supplementing an HF diet with enzymes in growing pigs. Experiment one investigated HF and enzyme supplementation on energy and nutrient digestibility, digesta volatile fatty acid (VFA) concentrations, and gut microbial profile in pigs. Compared with the HF diet, enzymes improved dry matter, starch, energy and some amino acid (AA), but not nitrogen digestibility. Further, the enzymes stimulated the growth of gut bacterial groups, which have xylanolytic and cellulolytic properties in the HF-fed pigs, but enzymes did not influence digesta VFA concentration or fiber fermentation. Experiment 2 evaluated the effects of enzyme supplementation on growth performance, glucose uptake in jejunum tissue samples mounted in Ussing chambers, and intestinal nutrient transporter mRNA levels in pigs. Diet had no effect on feed intake and jejunal glucose uptake. The enzymes influenced nutrient transporter mRNA levels but did not improve pig growth rate and feed efficiency relative to the HF diet. The third experiment investigated the effect of supplementing the HF diet with enzymes on postprandial portal vein-drained viscera (PDV) nutrient fluxes and energy expenditure (measured as O2 consumption) by the PDV and whole-animal in pigs. Diet had no effect on energy expenditure. The HF diet reduced portal glucose, VFA and essential AA absorption and insulin production. Enzyme supplementation improved portal glucose and VFA absorption, but not essential AA absorption and insulin production. Overall, improvements in nutrient utilization due to enzyme supplementation did not improve the growth rate of pigs, which appears to be due to the lack of enzyme effect on essential AA and energy use by the PDV and insulin production