Clostridioides difficile infection (CDI) remains a leading cause of antibiotic-associated diarrhea worldwide, with recurrent episodes representing the most challenging aspect of disease management. Results from randomized controlled trials, multicenter cohorts, and systematic reviews on CDI demonstrate that fecal microbiota transplantation (FMT) achieves cure rates of about 80-90% and markedly reduces recurrence episodes. This review aimed to present an update on the clinical implementation of FMT for CDI treatment, including patient selection, risk stratification, donor screening, recipient preparation, delivery routes, and outcome monitoring. Data obtained from mechanistic studies showed that FMT can cause restoration in gut microbiota structure and diversity, promote butyrate- and secondary bile acid-producing microbial taxa, suppression in C. difficile germination, and modulation in mucosal and systemic immune responses. We also summarized other microbiome-based strategies, including defined microbial consortia, engineered live biotherapeutics, postbiotics, and phage therapy, which aim to replicate the ecological and functional benefits of FMT with greater standardization and safety. Ultimately, we investigated outstanding problems, such as donor variability, transmission of multidrug-resistant organisms, long-term ecological concerns, and global inequities in access, while considering potential paths to precision-guided and scalable microbiota-based therapeutics.