Rheumatoid arthritis (RA) is one of the diseases autoimmune systemic progressively characterized by inflammation of the membrane synovial that coating joints. Methotrexate (MTX) and Adalimumab are one of the drugs that are commonly used in Rheumatoid arthritis treatment. This study is aimed to look at the effectiveness and safety of both either in monotherapy and a combination of them. This study is a review of the article of experimental studies with data retrieval retrospectively on a database that has been set, namely PubMed, Google Scholar, and Portal Garuda were conducted for 6 mo. The use of adalimumab showed improvement based on the value DAS28-4(ESR) and HAQ-DI when compared with methotrexate. The side effects caused by MTX showed the risk was more than 2% than adalimumab. Several drug carriers are determinants of therapeutic efficacy, such as sRNA (small interfering-RNA), LPNP (hybrid lipid-polymers nanoparticles), FRβ (Folate-receptor β), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B-cells), β-GP (β-Glycerophosphate). The use of adalimumab monotherapy has slightly better effectiveness than methotrexate but has more diverse side effects but less risk. The use of the combination does not have a significant difference, but the risk of side effects from both is lower than when used alone.