Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the synovial joints. RA has well-known clinical manifestations and can cause progressive disability and premature death along with socioeconomic burdens. Interleukin-6 (IL-6) has been implicated in the pathology of RA where it can stimulate pannus formation, osteoclastogenesis, and oxidative stress. Flavonoids are plant metabolites with beneficial pharmacological effects, including anti-inflammatory, antioxidant, antidiabetic, anticancer, and others. Flavonoids are polyphenolic compounds found in a variety of plants, vegetables, and fruits. Many flavonoids have demonstrated anti-arthritic activity mediated mainly through the suppression of pro-inflammatory cytokines. This review thoroughly discusses the accumulate data on the role of flavonoids on IL-6 in RA.