Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with matrix metalloproteinase (MMP)-3, leading to destruction of the cartilage. The objective of this study was to investigate and discuss the suitability of the 35 medicinal plants as therapeutic candidates to treat RA. Fibroblast-like synoviocytes (FLSs), derived from patients with RA, were adjusted to 2 x 10(6) cells/mL in a 24-well plate and pretreated with the distilled water extracts of the 35 plants (1, 10, and 100 mu g/mL) for 1 h followed by interleukin-1 beta (IL-1 beta) (1 ng/mL) for 24 h. The concentration of MMP-3 was then determined using a Duoset ELISA Kit. The six plants (Artemisiae Capillaris Herba, AC; Bambusae Caulis In Taeniam, BC; Cassiae Semen, CS; Corni Fructus, CF; Leonuri Herba, LH; Schizonepetae Spica, SS) showed no toxicity, including MMP-3. The MMP-3 level was increased by 3.38-fold (212.23 mu g/mL) in IL-1 beta-stimulated FLSs. The IL-1 beta-induced MMP-3 level was significantly and dose-dependently reduced by > 50% by the six plants (P < 0.01: at 100 mu g/mL of CS and LH, P < 0.001: at 10 mu g/mL of all plants, and at 100 mu g/mL of AC, BC, CF, and SS). This is the first study on the MMP-3 inhibitory effect of the examined plants in FLSs isolated from RA patients. From our original research, the six candidate plants were identified.