Patients with chronic, painful diseases often seek alternative therapy. The purpose of this study was to investigate the potential of hydroalcoholic extract of Zingiber officinale rhizomes (Z. officinale extract) to ameliorate inflammatory process in rat collagen-induced arthritis. Our results show that Z. officinale extract in doses higher than 50 mg/kg/day intraperitoneally starting from the dose of booster immunization and for 26 days can ameliorate the clinical scores, disease incidence, joint temperature and swelling, and cartilage destruction, together with reduction of serum levels of interleukin (IL)-1beta, IL-2, IL-6, tumour necrosis factor-alpha, and anti-CII antibodies. Moreover, Z. officinale extract at the dose of 200 mg/kg/day was superior to 2 mg/kg/day of indomethacin at most of the measured parameters. These observations might make Z. officinale extract a good alternative to non-steroidal anti-inflammatory drugs for patients with rheumatoid arthritis.