Toxin-mediated damage caused during Clostridioides difficile infection (CDI) is primarily observed in the colon, with significant injury to intercellular-junctions, polarity determinants, and stem cell niches of the colonic lining. These effects have been well reported during acute infection. However, the impact of CDI post‑infection and beyond the colonic lining is less clear. Using a novel CDI recovery mouse model, we report via histopathological and transcriptomic analyses that CDI greatly impairs the reparative ability of the colonic lining post infection, which appears to correlate with the disruption of stem cell regenerative capacity. Furthermore, we observe via contractility studies and immunofluorescence that CDI induces gut dysmotility and dysfunction by damaging the enteric nervous system, which coordinates peristaltic gut movements and secretes niche stem cell supportive factors. This improperly repaired and dysfunctional gut can consequently trigger systemic complications in extraintestinal organs as far as the thymus. Altogether, the perturbation of gut and extraintestinal functions may also contribute to CDI recurrence, which is readily experienced by patients. Thus, our findings indicate a novel mechanism wherein enteric pathogens impede motility, function, and the repair process of the host to increase the severity of illness and propagate disease. Such findings provide insight into the impact of enteric infections at and beyond the site of local damage as well as the effectiveness and appropriateness of current treatments. Importantly, these findings will lay the foundation for novel therapies to enhance gut recovery and motility, circumventing the reliance on antibiotics and potentially reducing the incidence of recurrent CDI.