Recently, our group’s review manuscript, "Recent development of small-molecular inhibitors against Clostridioides difficile infection" has been accepted by Bioorganic Chemistry. In this review, we have summarized small-molecules for treating Clostridioides difficile in detail to provide guidance for clinical treatment of Clostridioides difficile. This work was completed under the guidance of Dr. Wang Hong, Dr. Wu Qiang and Dr. Chen Jianwei.