Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) possesses anti-inflammatory effects, attributed to the main constituent andrographolide proposed as alternative in the treatment of autoimmune disease. A prospective, randomized, double blind, and placebo-controlled study in patients with rheumatoid arthritis (RA) was performed. Tablets (Paractin®) made of an extract of A. paniculata (30% total andrographolides) were administered three times a day for 14 weeks, after a 2-week washout period to 60 patients with active RA. The primary outcomes were pain intensity measured using a horizontal visual analog pain scale (VAPS). In addition, ACR, EULAR, and SF36 clinical parameters were recorded. The intensity of joint pain decreased in the active vs placebo group at the end of treatment, although these differences were not statistically significant. A significant diminishing for week in tender joint −0.13 95% confidence interval (CI; −0.22 to 0.06; p = 0.001), number of swollen joints −0.15 95%CI (−0.29 to −0.02; p = 0.02), total grade of swollen joint −0.27 95%CI (−0.48 to −0.07; p = 0.010), number of tender joints −0.25 95%CI (−0.48 to −0.02; p = 0.033), total grade of swollen joints −0.27 95%CI (−0.48 to −0.07; p = 0.01), total grade of tender joints −0.47 95%CI (−0.77 to −0.17; p = 0.002) and HAQ −0.52 95%CI (−0.82 to −0.21; p < 0.001) and SF36 0.02 95%CI (0.01 to 0.02; p < 0.001) health questionnaires was observed within the group with the active drug. Moreover, it was associated to a reduction of rheumatoid factor, IgA, and C4. These findings suggest that A. paniculata could be a useful “natural complement” in the treatment of AR; however, a larger trial and a more extended period of treatment is necessary in order to corroborate these results.