Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a complex condition marked by chronic inflammation of the gastrointestinal tract. Its heterogeneity in clinical presentation, etiology, disease progression, and response to treatment make IBD particularly challenging to diagnosis and manage effectively. Growing evidence has shown that microRNAs (miRNAs) are important regulators of gut physiology, and several have been implicated in the pathobiology of adult CD. Our lab and others have investigated miRNAs as potential diagnostic markers, prognostic indicators, and candidate therapeutic targets in IBD. Although these studies represent exciting advances, a major limitation is that they pertain only to adult CD. Very few studies have been conducted for pediatric CD. To address this gap in the field, my doctoral research sought to identify specific miRNAs that uniquely mark pediatric CD. Through this study, a miRNA (miR-29) was identified as a distinguishing feature in pediatric CD that was significantly elevated in diseased patients compared to non-IBD controls. The increased expression of miR-29 was highly predictive of disease severity. When miR-29 was overexpressed in a mouse model, there was increased inflammation and loss of Paneth cells, which are critical for maintaining intestinal homeostasis. These results were also confirmed in patients with elevated miR-29 levels. This work strongly supports the potential for miR-29 and other miRNAs as prognostic indicators of disease severity in pediatric CD. In a subsequent study I sought to identify novel markers associated with disease phenotypes in a similarly understudied cohort of adult UC patients with refractory disease. Using comprehensive miRNA and gene profiling in samples obtained at time of surgery, one particular miRNA (miR-375) was found to be a strong candidate marker of severe UC that may provide potential mechanistic insight to refractory disease. Identifying the genetic targets of the miRNA uncovered a key gene (CADM1) as a potent mediator of pro-inflammatory signaling pathways that shows potential as a diagnostic and therapeutic target for IBD. Together, the results presented in this dissertation provide novel insights to the potential clinical role of miRNAs IBD.