Introduction <p>Diabetes mellitus (DM) is associated with severe complications driven by chronic inflammation, which releases cytokines, chemokines, and adhesion molecules. Herbal medicines are gaining importance due to fewer drug-related adverse effects. Quercetin is a flavonoid with potent anti-inflammatory and antioxidant properties. This systematic review and meta-analysis aim to evaluate the impact of Quercetin on inflammatory markers in the animal model of diabetes.</p> Methods <p>A comprehensive literature search was conducted in PubMed, Embase, Web of Science and Google Scholar from inception to February 2025, to identify relevant preclinical studies. Diabetic rodents were included, whereas in vitro, ex vivo, and non-rodent studies were excluded. A meta-analysis using a random-effects model (RE) was performed to calculate standardised mean differences (SMD) with 95% confidence intervals. Methodological quality was assessed by sensitivity analyses, publication bias and SYRCLE risk of bias.</p> Result <p>The included 14 studies in this systematic literature review and meta-analysis indicates that Quercetin treatment significantly reduces the TNF-α (SMD: − 3.40, 95% CI − 5.17 to − 1.63) (<i>P</i> = 0.0002), IL-1β (SMD: − 1.57, 95% CI − 2.65 to − 0.49) (<i>P</i> = 0.004) and IL-6 (SMD: − 4.28, 95% CI − 5.86 to − 2.70) (<i>P</i> &lt; 0.00001). Possible publication bias and moderate-to-substantial heterogeneity (I²) were observed. The results remained unchanged after sensitivity analyses, trim-and-fill analyses.</p> Conclusion <p>The present meta-analysis demonstrates that Quercetin treatment significantly reduces the inflammatory markers in diabetic animal models. These findings provide a strong preclinical foundation for further clinical research, highlighting Quercetin as a potential treatment to mitigate inflammation-driven complications in diabetes.</p>