Rheumatoid arthritis (RA) is a progressive and chronic systemic autoimmune disease. However, currently treatment is often carried out using NSAIDs and corticosteroids. Although it reduces symptoms, this treatment has a high rate of side effects. This study aims to determine the anti-inflammatory property of Curcuma heyneana so that it can be used as an alternative treatment for RA. Based on author knowledge, this study on C. heyneana from the Indonesian region for the treatment of RA is still limited. C. heyneana’s rhizome was extracted by maceration with ethanol followed by fractionation process using n-hexane, ethyl acetate, and n-butanol. The anti-inflammatory invitro activities were determined by heat-induced hemolysis, effect on protein denaturation, and cyclooxygenases (COX) inhibition assay. Molecular docking of major predictive compounds was performed by AutoDock Vina. The results showed that some fractions of C. heyneana contained terpenoids, flavonoids, and alkaloids. The ethyl acetate fraction exhibited the highest anti-inflammatory activity, which was attributed to the presence of curcuminoids. Molecular docking studies further confirmed the potential of demethoxycurcumin, a curcuminoid identified in the ethyl acetate fraction, to inhibit COX-2. These findings suggest that C. heyneana, particularly its previously unreported curcuminoid-rich fractions, holds promise as a natural anti-inflammatory agent. Further research is warranted to explore the therapeutic potential of this plant in the management of RA and other inflammatory disorders.