Functional AA (FAA), the need for which dramatically increases in response to immune response, are mobilized through the degradation of muscle protein. Dietary FAA supplementation has been hypothesized to enhance the immune system or fortify the health of weaned piglets, thereby improving protein accretion and growth performance. The objective of this study was to evaluate the efficacy of dietary FAA supplementation in weaned pigs in relation to different weaning stressors. In Experiments 1 and 2, dietary Thr supplementation was evaluated in relation with diet complexity. Dietary L-Thr supplementation enhanced the intestinal morphology (villus height and number of goblet cells) and microbial metabolites in the gut (short-chain fatty acid concentration), as well as body protein mass. The benefits of supplementation were greater with a simple diet than with a complex diet. However, the inflammation (the increase in interleukin-6 and interleukin-10) caused by feeding a simple diet could not be modulated with L-Thr supplementation. In Experiment 3, dietary sulfur amino acids supplementation was investigated in pigs under oxidative and inflammatory status that were induced by a lipopolysaccharide challenge. Dietary DL-Met supplementation at 0.1% failed to restore the intestinal morphology, permeability, and redox status impaired by a lipopolysaccharide (LPS) challenge, but it improved the hepatic glutathione levels and inflammatory responses. By contrast, dietary L-Cys supplementation at 0.1% improved intestinal morphology, permeability, and redox status of LPS-challenged pigs, restoring them to a level comparable to the sham-challenged control. Supplementation with combined DL-Met and L-Cys showed antagonistic effects on the inflammatory response, intestinal morphology, and redox status. Experiment 4 explored the effect of dietary Val supplementation on inflammatory status and intestinal microbial composition in weaned pigs raised in low or high sanitary condition. Dietary L-Val supplementation beneficially modulated intestinal bacteria composition and microbial metabolites in the gut and suppressed a systemic inflammatory response, regardless of the sanitary condition. In Experiment 5, the supplementation of an AA blend, including Met, Thr, Trp, Val, and Ile, throughout a five-week nursery production period enhanced growth performance for phases I and III. However, the withdrawal of supplementation after phase I led to a lower gain to feed ratio compared with the continuous supplementation. Overall, dietary FAA supplementation enhanced the immune system or fortified the health of weaned piglets, thereby improving protein accretion and growth performance. Dietary FAA supplementation to a weaner pig diet can be a beneficial nutritional strategy to cope with post-weaning stress (e.g., dietary stress, oxidative stress, inflammation, and poor sanitary condition) by enhancing intestinal integrity and barrier function, antioxidant defense system, and N utilization and by modulating the microbial profile and metabolites in the gut