Rheumatoid arthritis (RA) is a chronic autoimmune disorder that activates arthritogenic immune responses, along with many of the systemic inflammatory cascades that result in synovitis and the progressive irreversible destruction of affected joints. Studies have demonstrated the pathogenic role of some biomolecules and autoantibodies in RA disease. Some other markers, like erythrocyte sedimentation rate (ESR), acute phase reactant protein (CRP), and rheumatoid factor (RF), have also been used successfully to diagnose and treat RA. These are the anticyclic citrullinated peptide (ACPA) autoantibody, tumor necrosis factor-alpha (TNFα), and interleukin 1 and 6 (IL-1, IL-6). Many others are still under study. In this review, we focused on a few biomolecules that could either directly or indirectly contribute to the pathogenesis of RA, aiming to demonstrate their diagnostic characteristics and capacity to forecast the disease. These are Galectin-3 (Gal-3), matrix metalloproteinase-3 (MMP-3) and toll-like receptor 2 (TLR-2). After reviewing peer-reviewed studies from 24 years ago, we concluded that these markers could potentially serve as prognostic factors for RA disease activity in the future and have reasonable diagnostic power. We believe that combining these markers with traditional ones could enhance the accuracy and clarity of clinical diagnosis, as well as track the effectiveness of current therapies.