Clostridioides difficile bacteria can cause life-threatening diarrhea and colitis owing to limited treatment options and unacceptably high recurrence rates among infected patients. This necessitates the development of alternative routes for C. difficile treatment. Drug repurposing with new indications represents a proven shortcut. Here, we present a refined focus on 16 FDA-approved drugs that would be suitable for further development as potential anti-C.-difficile drugs. Of these drugs, clinical trials have been conducted on five currently used drugs; however, ursodeoxycholic acid is the only drug to enter Phase IV clinical trials to date. Thus, drug repurposing promotes the study of mechanistic and therapeutic strategies, providing new options for the development of next-generation anti-C.-difficile agents.