The objective of Study 1 was to assess the effect of a novel corn-expressed phytase (CEP) on growth, nutrients digestibility, bone characteristics, and fecal microbiota of pigs fed with very low-protein, -calcium (Ca) and -phosphorous (P) diets. Forty-eight barrows were subjected to 6 groups for 4 weeks: positive control-adequate protein, negative control-reduced protein (NC), NC + low-dose CEP, i.e., 2000 FTU/kg (LD), NC + high-dose CEP, i.e., 4000 FTU/kg (HD), LD with 0.12% unit reduced Ca and 0.15% unit reduced available P, and HD with 0.12% unit reduced Ca and 0.15% unit reduced available P. Supplementation of protein-restricted diets with a CEP decreased their negative effects on average daily gain and gain:protein ratio, increased the digestibility of Ca and P regardless of the levels of these minerals in the diet, improved bone characteristics and produced differential effects on fecal bacterial population. The objective of Study 2 was to investigate whether supplementation of very low protein (VLP), low-Ca, and low-P diets with a CEP can influence the blood amino acids (AA) and proteomics profiles in pigs. The experiment design and diets were the same as Study 1. CEP improved the blood profile of some essential AA and affected the expression of proteins involved in regulation of growth in pigs fed with VLP diets. Further, alterations in expression of serum proteins that are important for bone mineralization and muscle structure development likely contributed to beneficial effects of CEP on growth, body composition and bone measurements in pigs fed with VLP diets. The objective of Study 3 was to assess the effect of a phytogenic water additive (PWA) on growth performance and underlying factors involved in pigs fed with low-protein (LP)/high-carbohydrate diets. Forty-eight weaned barrows were allotted to 6 treatments for 4 weeks: control (CON) diet-no PWA, CON diet-low dose PWA (4 mL/L), CON diet-high dose PWA (8 mL/L), LP diet-no PWA, LP diet-low dose PWA and LP diet-high dose PWA. In this study, PWA improved the performance of weaned pigs fed with protein-adequate diets likely through increased blood essential AA and affected the muscle composition when dietary protein was deficient.