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Chronic inflammation plays a central role in the pathophysiology of various non-communicable diseases. Dietary interventions can reduce inflammation, in part due to their effect on the gut microbiome. This systematic review aims to determine the effect of dietary interventions, specifically fiber intake, on chronic inflammatory diseases and the microbiome. It aims to form hypotheses on the potential mediating effects of the microbiome on disease outcomes after dietary changes. Included were clinical trials which performed a dietary intervention with a whole diet change or fiber supplement (>5 g/day) and investigated the gut microbiome in patients diagnosed with chronic inflammatory diseases such as cardiovascular disease (CVD), type 2 diabetes (T2DM), and autoimmune diseases (e.g., rheumatoid arthritis (RA), inflammatory bowel disease (IBD)). The 30 articles which met the inclusion criteria had an overall moderate to high risk of bias and were too heterogeneous to perform a meta-analysis. Dietary interventions were stratified based on fiber intake: low fiber, high fiber, and supplemental fiber. Overall, but most pronounced in patients with T2DM, high-fiber plant-based dietary interventions were consistently more effective at reducing disease-specific outcomes and pathogenic bacteria, as well as increasing microbiome alpha diversity and short-chain fatty acid (SCFA)-producing bacteria, compared to other diets and fiber supplements.