Abstract: Background and Objective: Etlingera rubroloba A.D. Poulsen (E. rubroloba) is a plant endemic to South-East Sulawesi which is used empirically by local people as a pain reliever for joints and to increase endurance after typhoid fever. This study aimed to determine the antioxidant and anti-inflammatory activity of the ethanol extract stem of E. rubroloba. Materials and Methods: The stem of the ethanol extract of E. rubroloba with evaluated for antioxidants using the FRAP method and anti-inflammatory activity with the parameter level of Tumor Necrosis Factor-Alpha (TNF-α) in vivo by using 6 groups of rats, namely the normal, the negative (Na-CMC 0.5%), the positive control (Diclofenac sodium) and the ethanol extract group at doses of 200, 300 and 400 mg kg–1 b.wt. Results: The results of this study indicated that the antioxidant activity value of the IC50 ethanol extract was 12.720±0.12 μg mL–1 and ascorbic acid (vitamin C) as a standard control was 3.14±0.12 μg mL–1. The TNF- α normal group (7.83 pg mL–1), negative control (250.92 pg mL–1), positive control (123.66 pg mL–1), treatment group dose 200 (192.20 pg mL–1), 300 (97, 95 pg mL–1) and 400 mg kg–1 b.wt. (28.78 pg mL–1). Conclusion: This study concluded that the ethanol extract of the stem of E. rubroloba has a very strong antioxidant activity and is an anti-inflammatory which is the best in reducing levels of TNF-α at a dose of 400 mg kg–1 b.wt.