Crohn’s disease (CD) is a chronic, recurrent, immune-mediated inflammatory bowel disease that demonstrates a spectrum of intestinal and extra-intestinal manifestations. The pathogenesis of CD is multifactorial and involves a complex interplay between environmental and microbiological factors in a genetically susceptible host. There is robust evidence suggesting the role of gut microbial dysbiosis in the development as well as exacerbation of CD by immune dysregulation and alteration in the immune microbiota crosstalk. Patients with CD show reduced commensal microbial diversity, along with increased numbers of pathogenic Enterobacteriaceae and Proteobacteriaceae. Faecalibacterium prausnitzii, an anti-inflammatory molecule-producing bacteria, is also seen in reduced numbers in patients with CD and is associated with an increased risk of recurrence. There has been a paradigm shift in the management of patients of CD, from controlling symptoms to controlling inflammation and promoting mucosal healing. Current treatment strategies aim to replace, remove, reset, or redesign the gut microbiota for the therapeutic benefits of patients with CD. These include microbial restoration therapies such as dietary modification, the use of pre-, pro-, and postbiotics, and fecal microbiota transfer (FMT). This chapter focuses on the role of gut microbiota in the pathophysiology of CD and the emerging concepts in microbial therapeutics.