<p><i>Rosa moschata</i> is well known plant for its high levels of nutrients, including quercetin and phenolic compounds, which are believed to reduce inflammation. The purpose of the current study was to assess the anti-polyarthritis potential of <i>R. moschata</i> leaf extract (RMLE) utilizing complete Freund’s adjuvant (CFA) in rats. Hydro ethanol extract was prepared by microwave assisted extraction method and its phytochemical characterization was performed by GCMS analysis. Six groups of albino rats (<i>n</i> = 6) were made. Polyarthritis was induced by injecting 0.1 mL of CFA into the back paw of rats. Extract treated groups received RMLE at 150, 300, and 600&#xa0;mg/kg p.o. for 4 weeks. The body weight, paw diameter, arthritic index was determined at first on 3^rd day then on every week till 4th week of the study. On completion of the study, biochemical, hematological, radiographic and histopathological studies were performed, and oxidative stress markers were measured. qPCR was done to quantify the RMLE impact on inflammatory biomarkers. Results showed improvement in the polyarthritis symptoms by decreasing the paw diameter, arthritic index, rheumatoid factor and C-reactive protein dose dependently. The different oxidative stress markers level was also found to be normalized after plant extract treatment. Histopathological findings displayed improvement in inflammation and synovial hyperplasia in ankle joints in RMLE treatment groups. Radiographical analysis showed improvement in inflammation, joint effusion and bone atrophy in the RMLE groups. qPCR results exhibited upregulation of anti-inflammatory while downregulation of pro-inflammatory in the RMLE groups. According to the conducted study, RMLE may be utilized as a natural anti-polyarthritis cure and as a base for new drug development to treat polyarthritis.</p> Graphical abstract <p></p>