Ulcerative colitis is a colonic inflammatory disease that is long-term. Inflammatory, oxidative stress, and molecular activation biomarkers could enhance the evaluation of the disease. The circulation of the miR-21 is also relevant in mucosal inflammation and its clinical significance in ulcerative colitis is yet to be determined. This study tries to measure circulating miR-21, oxidative stress biomarkers and inflammatory indices in patients with ulcerative colitis and to test associations between them and disease activity, fecal calprotectin and composite inflammatory oxidative stress indices. This case–control study included 121 adults recruited at the Teaching Hospital for Digestive and Liver Diseases, Medical City, Baghdad, from 9 February 2025 to 23 October 2025. A total of 88 patients who had confirmed ulcerative colitis and 33 healthy controls were included in the sample. There were active disease and remission. Standard immunochemical and colorimetric measures were taken of serum CRP, IL-6, MDA, TAC and SOD. qRT-PCR was used to determine the levels of circulating miR-21. Fecal calprotectin and Mayo endoscopic subscore also were noted. Correlations, group comparisons, effect sizes, ROC analysis and exploratory regression models were carried out. Compared with controls, patients with ulcerative colitis had higher CRP, IL-6, MDA, miR-21, fecal calprotectin, IOSI, and Advanced IOSI, and lower TAC and SOD (all p < 0.001). CRP, IL-6, MDA, fecal calprotectin, IOSI, Advanced IOSI, TAC and SOD were significantly higher in active disease than remission (all p < 0.001). The level of circulating miR-21 was higher in comparison to controls but lower in active disease than in remission (p = 0.026). There was a strong correlation between IOSI and Advanced IOSI and fecal calprotectin. There was very high discrimination of a number of markers in this resultsset using ROC including CRP, IL-6, fecal calprotectin, IOSI and Advanced IOSI. The results indicate that there is a strong association between ulcerative colitis, systemic inflammation and oxidative imbalance. It seems that circulating miR-21 can be relevant, yet its activity can vary in response to activity states, and be altered by treatment. Composite inflammatory-oxidative stress indexes were well-performing and potentially provide a convenient summary of multi-marker perturbation. Clinical adoption still needs to be externally validated.