Compounds in garlic have been shown to contain anti-inflammatory, antioxidant, and immune modulatory properties that may be able to mitigate the effects of nursery pig stressors. The objective of the current experiment was to determine if oral gavage of garlic-derived diallyl disulfide (DADS) and diallyl trisulfide (DATS) could mitigate the effects of a 24-h postweaning feed + water deprivation event in nursery pigs. Pigs (6.0 ± 0.05 kg and 21 d old) were allotted to 4 treatments in a randomized complete block design at weaning with 8 replicate pens per treatment that consisted of with or without a 24-h postweaning feed + water deprivation event and with or without an oral gavage containing 3.6 mg DADS + DATS/kg BW. Growth performance and morbidity were recorded throughout the experiment, and on 1, 6, and 21 d after weaning, 1 pig per pen was selected, blood was collected, the pig was euthanized, and a segment of the distal ileum was subsequently excised for morphological and gene and protein expression measurements. Mucosal gene expression was conducted by reverse transcription PCR for immune, antioxidant, and cellular integrity markers. Furthermore, activity of mucosal superoxide dismutase was measured by colorimetric assay. Immediately following the feed + water deprivation event, there was a decrease (P < 0.01) in growth performance and an increase (P = 0.01) in serum cortisol. The feed + water deprivation event tended (P = 0.10) to decrease ileal villus height and supplementation of DADS + DATS by oral gavage increased (P = 0.03) villus height 1 d after weaning. Supplementation of DADS + DATS by oral gavage decreased (P = 0.03) and tended to decrease (P = 0.08) gene expression of SOD on 6 and 21 d after weaning, respectively. Furthermore, at 1 d after weaning, ileal mucosa SOD activity was decreased (P = 0.01) by the feed + water deprivation and increased (P = 0.04) by oral supplementation of DADS + DATS. Expression of the tight junction genes ZO-1 and OC were reduced (P ≤ 0.05) due to the feed + water deprivation event 1 d after weaning. Results from the current study show that an acute feed + water deprivation event can impact growth performance, intestinal characteristics, and antioxidant status in nursery pigs, which can be partially mitigated by oral supplementation of garlic compounds DADS + DATS.