Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired diarrhea and has become a major challenge in the global public health field. In recent years, it has been found that nutrients and gut microbes play key roles in regulating growth, metabolic activity, and virulence expression of Clostridioides difficile. However, current research focuses on the independent effects of a single nutrient or gut microbe, systematic understanding on the interactions between them is still lacking. This paper reviews the specific effect of different nutrients on Clostridioides difficile, explores how other gut microbes inhibit the growth of Clostridioides difficile by competing or metabolizing nutrients. In addition, this paper also discusses the application of emerging technologies in CDI research and their potentiality in clinical intervention strategies. Future research needs to integrate multi-omics data and artificial intelligence analysis, deeply analyze the complex interactive network of nutrient-microbe-host, and provide new ideas for precise prevention and treatment of CDI.