Rheumatoid arthritis (RA) is an autoimmune, systemic disease mainly affecting joints. Presently, there is no specific treatment/ drug available for curing RA except few supportive medicines. Therefore, the focus has been diverted on medicinal plants for the treatment of such diseases. Choerospondias axillaris commonly known as Lupsi/Lapsi and have been reported to have several properties for treating various diseases.The present study has been undertaken to explore the anti-inflammatory effects of Choerospondias axillaris fruit extract on synoviocytes (FLS) and collagen-induced arthritis (CIA) rat model.Methanolic extract of the Choerospondias axillaris fruit was used for checking phytochemical, antioxidant and anti-inflammatory properties. Antioxidant activity of Choerospondias axillaris fruit was measured via free radicals scavenging assays and bioactive compounds were identified via LC-MS/MS analysis. Anti-inflammatory effect was investigated in RA and Osteo arthritis (OA) primary cells and also in Collagen Induced Arthritis (CIA) rat models. Further, the medicinal properties of anti-inflammatory bioactive compounds were supported by docking studies.In-vitro and in-vivo studies showed significant decrease in the levels of inflammatory cytokines. Docking analysis revealed that quercetin inhibits TNF-α having -9.1 kcal/mol binding energy and 10.13 µM inhibitory constant. Quercetin also inhibits IL-6 having -6.6 kcal/mol binding energy and 21.9 µM inhibitory constant.Observed results suggests that the underutilized fruit Choerospondias axillaris can be used to reduce the inflammation of inflammatory diseases like RA.