The effects of both live and heat‐killed states of Lactiplantibacillus plantarum MWFLp‐182 (L. plantarum MWFLp‐182) isolated from the faeces of long‐lived humans on preventing and relieving Salmonella infection were studied. Evaluation methods included RT‐qPCR measurement of inflammatory factors, histopathological analysis and non‐targeted metabolomics. The results showed that L. plantarum MWFLp‐182 in both states improved body weight loss, organ swelling and ileocolon pathological damage. They also protected against Salmonella infection by regulating key KEGG enrichment pathways and the expression levels of TNF‐a and IL‐6. It is worth noting that the function of live bacteria was better than that of heat‐killed bacteria.