Colitis caused by non-typhoidal Salmonella (NST) infection is increasingly serious and widespread, so new effective treatment strategies with little or no side-effects are urgently needed. Our previous research found that phenyl lactic acid (PLA) derived from Lactobacillus plantarum ZJ316 can effectively inhibit Salmonella enterica Typhimurium (S. Typhimurium). In this study, we further investigated the protective effects of this PLA against S. Typhimurium-induced colitis in mice. An infection model was established using female C57BL/6J mice by oral administration of 10⁹ CFU mL⁻¹ of S. Typhimurium, and PLA was supplied for 10 days after infection. In colitic mice, PLA administration reduced the disease activity index, prevented the colon shortening and spleen enlargement, decreased liver enzyme (AST and ALT) activities, and alleviated the colonic tissue damage. RT-qPCR analysis showed that PLA significantly down-regulated the levels of NF-κB, TLR4 and pro-inflammatory cytokines (IFN-γ, IL-1β and TNF-α), but stimulated the mRNA expression of the anti-inflammatory cytokine IL-10. Changes in intestinal microecology were analyzed by 16S rRNA sequencing. PLA modulated colonic microbiota dysbiosis by increasing the abundance of Lactobacillus, Butyricicoccus and Roseburia, and reducing Salmonella and Alloprevotella at the genus level. In addition, PLA significantly increased the concentrations of short-chain fatty acids (SCFAs) in the colon, especially propionic acid and butyric acid. These findings revealed that PLA has potential benefits on alleviating S. Typhimurium-induced colitis mainly through intestinal microbiota regulation and inflammation elimination, providing a new perspective for the NTS infection treatment strategy.