<p>Autoimmune diseases are chronic conditions that arise from the loss of immune tolerance toward the body’s own tissues. Current therapeutic options are often associated with adverse effects and limited long-term efficacy. Quercetin, a naturally occurring flavonoid with well-documented antioxidant, anti-inflammatory, and immunomodulatory properties, has emerged as a potential therapeutic candidate for autoimmune conditions. This systematic review aimed to evaluate the current evidence on the pharmacological effects and therapeutic potential of quercetin in autoimmune diseases. Original in vitro studies using human-derived cell models and human clinical (in vivo) studies published in English from 2014 onwards that investigated quercetin’s effects on autoimmune conditions were included, while reviews, non-English publications, and studies lacking mechanistic insights were excluded. Comprehensive searches across three electronic databases – PubMed, Scopus, and the Cochrane Library, supplemented by manual reference screening, resulted in the inclusion of thirteen studies for qualitative synthesis. Quercetin consistently demonstrated beneficial effects, including attenuation of oxidative stress, suppression of pro-inflammatory cytokines, and modulation of immune-related signaling pathways. Several clinical studies reported that quercetin alleviated disease severity and reduced tissue inflammation. Overall, quercetin exhibits pleiotropic mechanisms of action that collectively contribute to its immunomodulatory and protective effects in autoimmune diseases. However, the limited number of clinical trials and heterogeneity in study designs highlight the need for further standardized and well-controlled investigations to validate its therapeutic potential.</p> Graphical Abstract <p></p>