During commercial pig production, weaning is a major stressor that disrupts the gut microbiome, compromises intestinal barrier integrity, and increases the susceptibility of piglets to pathogens. This often results in post-weaning diarrhoea (PWD), leading to growth retardation, morbidity, and economic loss. This study investigated the effects of dietary xylo-oligosaccharide (XOS) supplementation on the growth performance and gut health of 216 piglets with naturally occurring PWD. Piglets received either 0 (CON), 50 (XOS-50), or 500 (XOS-500) mg XOS/kg feed from weaning at 28 days of age (d1) for 54 days. XOS-500 significantly improved body weight at d22 and d54, but had no effect on average daily gain, daily feed intake (DFI), or feed conversion ratio. The intestinal microbiota alpha-diversity was unaffected by XOS, though jejunal beta diversity differed between CON and XOS-500 groups at d22. Jejunal Chao richness correlated positively with d54 body weight, while ileal Chao richness correlated negatively with DFI. was present in all diet groups but did not differ in abundance; however, the levels were negatively correlated with alpha diversity. XOSs increased (d22, d54) and (d22), while reducing spp. (d22). XOSs reduced jejunal goblet cell (GC) density at d22 but increased duodenal and jejunal GCs and reduced duodenal crypt depth at d54. XOSs upregulated the genes for the tight junction proteins CLDN2, CLDN3, ALPI, and ZO-1, while downregulating the cytokine IL-8. These findings highlight XOSs' potential to improve growth and gut health in weaning piglets with naturally occurring PWD, to maintain productivity and enhance welfare.