The rapid increase in microbial antibiotic resistance in Clostridioides difficile (C. difficile) strains and the formation of hypervirulent strains have been associated with a global increase in the incidence of C. difficile infection (CDI) and subsequently, an increase in the rate of recurrence. These consequences have led to an urgent need to develop new and promising alternative strategies to control this pathogen. Engineered probiotics are exciting new bacterial strains produced by editing the genome of the original probiotics. Recently, engineered probiotics have been used to develop delivery vehicles for vaccines, diagnostics, and therapeutics. Recent studies have demonstrated engineered probiotics may potentially be an effective approach to control or treat CDI. This review provides a brief overview of the considerations for engineered probiotics for medicinal use, with a focus on recent preclinical research using engineered probiotics to prevent or treat CDI. We also address the challenges faced in the production of engineered strains and how they may be overcome in the application of these agents to meet patient needs in the future.