This experiment investigated the effects of dietary supplementation with GutPlus® Virsorb probiotic on piglets infected with porcine epidemic diarrhea virus (PEDV). Seventy-two Duroc × Landrace × Yorkshire weaned piglets (21 days of age, 5.51 ± 0.44 kg) were randomly divided into: the CON1 group (negative control, basal diet), the CON2 group (positive control, basal diet), and the GutPlus® Virsorb group (basal diet + 500 g/t GutPlus® Virsorb). At 28 days of age, piglets in the CON2 and GutPlus® Virsorb groups received 40 mL PEDV (8.58 × 108 copies/mL) orally, while the CON1 group received an equivalent volume of sterile saline. The experiment lasted until 60 days of age. Dietary supplementation with GutPlus® Virsorb ameliorated the decrease in the average daily feed intake (ADFI) and the average daily gain (ADG) caused by PEDV infection. Compared with the CON2 group, GutPlus® Virsorb increased jejunal mucosa GPX and decreased jejunal mucosa MDA. Additionally, GutPlus® Virsorb decreased the mRNA expressions of IFN-β, TNF-α, and IL-6 in the jejunal mucosa. Compared to the CON2 group, GutPlus® Virsorb increased relative abundances of Lactobacillus, Prevotella, Akkermansia, and Butyricicoccus_A, while the relative abundance of Clostridium_P and Clostridium_T was reduced. In addition, GutPlus® Virsorb significantly increased the relative quantitative values of cis-cyclo (leucyl-tyrosyl), oxyphenbutazone, callicarpic acid B, and tilisolol. In conclusion, GutPlus® Virsorb improved the growth performance of PEDV-infected piglets, alleviated inflammation and intestinal damage by improving immunity, reduced PEDV copy number, increased antioxidant capacity, and improved gut microbiota structure and metabolite properties, showing a good protective effect against PEDV infection.