In this work,Lactiplantibacillus plantarum(L. plantarum) isolated from mice feces (LP-M) and pickles (LP-P) were chosen as the endogenous and exogenousL. plantarum, respectively, which were separately combined with chitosan oligosaccharides (COS) to be synbiotics. The anti-inflammatory activity of LP-M, LP-P, COS, and the synbiotics was explored using dextran-sodium-sulfate (DSS)-induced acute colitis mice, as well as by comparing the synergistic effects of COS with LP-M or LP-P. The results revealed thatL. plantarum, COS, and the synbiotics alleviated the symptoms of mice colitis and inhibited the changes in short-chain fatty acids (SCFAs), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-10, and myeloperoxidase (MPO) caused by DSS. In addition, the intervention ofL. plantarum, COS, and the synbiotics increased the relative abundance of beneficial bacteriaMuribaculaceaeandLactobacillusand suppressed the pathogenic bacteriaTuricibacterandEscherichia-Shigella. There was no statistically difference between LP-M and the endogenous synbiotics on intestinal immunity and metabolism. However, the exogenous synbiotics improved SCFAs, inhibited the changes in cytokines and MPO activity, and restored the gut microbiota more effectively than exogenousL. plantarumLP-P. This indicated that the anti-inflammatory activity of exogenous LP-P can be increased by combining it with COS as a synbiotic.