Inflammatory arthritis is a severe joint disease that causes long-lasting pain that reduces a patient's quality of life. Several commercial medicines have been used to reduce the inflammation in arthritis. However, they have side effects that affect other organs and increase the infection rate in the patient. Therefore, searching for alternative medicines from natural herbs to use as a substitute for chemical drugs and reduce the side effects of drugs has become the focus of investigation. DC., known as andaliman, is an endemic spice that originates from Tapanuli, North Sumatera (Indonesia). Our previous study confirmed that andaliman exerts anti-inflammatory and xanthin oxidase enzymatic inhibitory activities. Unfortunately, there are no in vivo studies on the efficacy of andaliman in reducing inflammation in arthritis. This research aimed to produce an andaliman extract rich in essential oils, to formulate andaliman extract in a nanoemulsion product, and to test their anti-arthritic and anti-inflammatory effects on suppressing the gene expression of inflammatory arthritis in vivo. Several steps were used to conduct this experiment, including andaliman extraction, bioactive compound identification, nanoandaliman formulation, in vivo inflammatory arthritis mice modeling using complete Freund's adjuvant (CFA), and gene expression quantification using quantitative PCR (qPCR). Andaliman extract and nanoandaliman effectively reduced arthritic scores in CFA-induced arthritic mice. Both treatments also demonstrated anti-inflammatory potential via blocking several arthritic inflammatory gene expressions from cartilage tissue and brain in CFA-induced mice. Nanoandaliman at low dose (25 mg/kg bw) exerted a higher suppressive effect against the gene expression of and compared to that of andaliman extract. At high dose (100 mg/kg bw), andaliman extract effectively inhibited the expression of and genes in arthritic mice. These data suggest that nanoandaliman may be an alternative, natural anti-arthritic and anti-inflammatory candidate for the management of inflammatory arthritis.