Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects mainly peripheral joints because of inflammation of the synovial membrane. Current treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, although effective, are associated with high costs and several adverse effects. In this context, natural products have emerged as promising alternatives because of their potential therapeutic effects and lower toxicity. The objective of this review was to identify and evaluate natural substances with potential applications in RA treatment on the basis of studies published between 2015 and 2020. A literature search was conducted in SciELO, PubMed, and Google Scholar using the keywords “rheumatoid arthritis”, “treatment”, “toxicity”, and “natural products”. Additionally, we applied in silico methods to predict pharmacokinetic and toxicological parameters using ADMET Predictor^® (Simulation Plus) and compared the results with those of commercial drugs such as diclofenac, ibuprofen, and naproxen. Target fishing (reverse docking) was also performed to identify possible molecular targets related to RA. Seven natural compounds were identified, mostly evaluated through in vivo studies. Among them, paeoniflorin, quercetin, resveratrol, and celastrol are in clinical phases and present potential as RA treatments. In silico analysis highlighted curcumin, tetramethylpyrazine, and resveratrol as the most promising candidates, with ADMET profiles comparable or superior to those of current NSAIDs. In conclusion, natural products represent viable alternatives for RA therapy. However, further studies are essential to better understand their safety, pharmacokinetics, and drug interactions to ensure their clinical applicability.