Rheumatoid arthritis (RA) is a chronic autoimmune mediated joint disease with severe complications affecting 1% of the population worldwide. Although the exact mechanism underlying the aggravation of RA remains unknown, its occurrence can lead to joint degradation and functional disability. Recent evidences have shown that the aberrant expression of microRNAs (miRNAs) play a prominent role in the furtherance of RA. Over the last decade, various intensive studies have validated different microRNAs to be good candidates for diagnostic purposes and for monitoring the disease progression in various inflammatory diseases. A deeper understanding of the molecular mechanism through which miRNAs amplify the production of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17), pro-inflammatory mediators, growth factors and MMPs will act as potential therapeutic targets. More importantly, several studies have briefly reported the crucial role of TLR dependent MAPK signaling pathway, which mediates the pathological features of RA. In this review, we summarize the recent findings and provide a detailed report of the molecular mechanism of microRNA along with the role of TLR/MAPK signaling pathway in RA. However, the major aim of this review is to correlate the aberrantly expressed microRNAs in TLR/MAPK pathway with various well reported bioactive compounds that can modulate these signaling pathways in rheumatoid arthritis. Targeting miRNA expression using specific bioactive compounds might be a potent and an effective target in RA treatment by suppressing the TLR/MAPK pathway. © 2017 Elsevier B.V.