Pork and pork products are recognised as vehicles of Salmonella Typhimurium infection in humans. Seaweed-derived polysaccharides (SWE) and galacto-oligosaccharides (GOS) have shown to exhibit antimicrobial, prebiotic and immunomodulatory activity. The objective of this study was to assess the effects of dietary GOS and SWE supplementation on reducing S. Typhimurium numbers and intestinal inflammation in vivo. In total, 30 pigs (n=10/treatment, BW 30.9 kg) were randomly assigned to three dietary treatments: (1) basal diet; (2) basal diet+2.5 g GOS/kg diet; (3) basal diet+SWE (containing 180 mg laminarin/kg diet+340 mg fucoidan/kg diet). Following an 11-day dietary adaptation period, pigs were orally challenged with 108 colony-forming units/ml S. Typhimurium (day 0). Pigs remained on their diets for a further 17 days and were then sacrificed for sample collection. The SWE supplementation did not affect S. Typhimurium numbers on days 2 and 4 post-challenge but reduced S. Typhimurium numbers in faecal samples collected day 7 post-challenge (−0.80 log gene copy numbers (GCN)/g faeces) and in caecal and colonic digesta (−0.62 and −0.98 log GCN/g digesta, respectively; P<0.05) compared with the control treatment. Lactobacillus numbers were increased in caecal and colonic digesta after GOS supplementation (+0.70 and +0.35 log GCN/g digesta, respectively; P<0.05). In colonic tissue, both GOS and SWE supplementation resulted in reduced messenger RNA expression levels of interleukin (IL)-6, IL-22, tumour necrosis factor-α and regenerating islet-derived protein 3-γ (P<0.05). It can be concluded that dietary supplementation of SWE reduced faecal and intestinal S. Typhimurium numbers compared with the basal diet, whereas dietary GOS supplementation increased Lactobacillus numbers in caecal and colonic digesta but did not affect S. Typhimurium numbers. Supplementation of GOS and SWE reduced the gene expression of pro-inflammatory cytokines in colonic tissue of pigs after the experimental S. Typhimurium challenge.