Abstract: Clostridioides difficile infection (CDI) is recognized as one of the urgent public health threats, and antibiotics such as metronidazole and vancomycin remain to be the first-line therapeutic agents for CDI. However, the extensive use of these antibiotics can disrupt intestinal flora balance, leading to CDI recurrence. So, maintaining the stability of intestinal microecology is an important alternative method for CDI prevention and treatment. Currently, microecological therapy has been approved by USA Food and Drug Administration as a novel approach for CDI management. In addition to the common fecal microbiota transplantation, microecological therapy may use a variety of emerging artificial microbial modulators, such as artificial microbiota (fecal derivatives), probiotics, engineered microorganisms, non-toxin C. difficile and phages. Each therapeutic modality shows distinct characteristics. It is expected that further advancements in microecological therapy research can make significant breakthroughs in the development of effective microbial modulators for CDI prevention and treatment.