Gynura procumbens (Lour.) Merr. has been used in some parts of Southeast Asia as a folk medicine to treat kidney diseases, diabetes mellitus, and hyperlipidemia. The present work was undertaken to prove the mechanisms of G. procumbens in the management of glomerular diseases. We investigated the effect of an aqueous extract of G. procumbens on cell proliferation, DNA synthesis, and the expressions of TGF-β1, PDGF-BB, CDK1, CDK2, and CDK4 in fetal bovine serum-activated human mesangial cells (MCs). The G. procumbens extract inhibited proliferation, DNA synthesis, expressions of PDGF-BB, CDK1, and CDK2 mRNA, and expression of TGF-β1 protein in MCs. The inhibitory effect of G. procumbens on MC proliferation may be mediated by suppression of PDGF-BB and TGF-β1 expressions and the modulation of CDK1 and CDK2 expression. Therefore, G. procumbens shows promise as an adjunct therapy in preventing progressive renal diseases.