The aim of the current study was to explore the effects and possible mechanisms of tripterygium glycosides tablet (TGT) in the treatment of active ankylosing spondylitis (AS). Thirty-six patients with active AS were given a 20 mg TGT treatment three times per day for 12 weeks, and 21 unrelated healthy controls were recruited as the control group. Efficacy measures included the Bath AS disease activity index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) prior and subsequent to TGT treatment. Serum dickkopf homolog 1 (DKK1) and interleukin-17 (IL-17) levels before and after TGT treatment were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA assay. The levels of several serum biomarkers were determined by ELISA, including receptor activator of nuclear factor κ-B ligand (RANKL), osteoprotegerin (OPG), bone alkaline phosphatase (BAP), bone morphogenetic protein-2 (BMP-2), matrix metalloproteinase-3 (MMP-3), cross-linked telopeptide of type II collagen (CTX-II), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2). After 12 weeks of TGT treatment, the BASDAI score of the patients was significantly reduced (P<0.05), their levels of ESR and CRP were significantly reduced to a normal level (P<0.05, P<0.05), RT-PCR and ELISA showed a significant increase in the level of DKK1 expression (P<0.05) and a significant decreased IL-17 expression (P<0.05), there was a significant increase in the expression of OPG, BAP and BMP-2 (P<0.01, P<0.01, P<0.01) and a significant reduction in the expression levels of RANKL, CTX-II. MMP-3, PGE2, and VEGF (P<0.01, P<0.01, P<0.01, P<0.05, P<0.01) compared with those of the controls. TGT is effective at improving the signs and symptoms of patients with AS through the regulation of serum biomarkers, and the mechanisms may be associated with the anti-inflammatory effect, inhibition of new bone formation and potential bone-protective effects.