Infant formulas (IFs), the only adequate substitute to human milk, are complex matrices that require numerous ingredients and processing steps. The objective was to understand how protein structure and quality within IFs impact plasma amino acid (AA) kinetics, gut physiology and microbiota. Four IFs containing whey proteins (WPs) with different origins and denaturation rates (IFs-A/-B/-C) or caseins with different organizations (IFs-C/-D) were produced as isonitrogenous despite slight differences of protein profile and AA concentrations. Both structure and in vitro digestion kinetics differed among IFs. Ten Yucatan mini-piglets (12- to 27-day-old) used as an infant model, received each IF during three days according to a Williams Latin square, followed by a two days wash-out period. Jugular plasma was regularly sampled from 10 min pre-prandial to 4 hours post-prandial on the third experimental day to measure free AA, urea, insulin and glucose concentrations. Data were analysed using a linear mixed model for repeated measures. IFs-A and -B, with higher WP denaturation rates, had significantly higher plasma total and essential AAs concentrations compared to IFs-C and -D, regardless of the time. Plasma threonine concentration was significantly different regardless of the time (A>B>C=D), probably resulting from glycomacropeptides presence in IFs-A and -B, known to cause increased threoninemia in infants. WP denaturation (IF-A) and casein supramolecular organization (IF-D) seemed to reduce AA catabolism. All these differences were present before meal ingestion indicating that a metabolic adjustment occurred during the dietary adaptation. Overall, this highlights the importance of the protein ingredient quality (WPs and caseins) within IFs on the plasma AA delivery, which can further impact protein metabolism, including the anabolic pathway of high importance at the infant stage. Whether it has consequences on the gut maturation and on the microbiota, an important actor within the microbiota-gut-brain axis is currently being investigated.