BACKGROUNDIndigo naturalis is effective against psoriasis. Indigo, indirubin and tryptanthrin, the main active components of indigo naturalis, have anti-inflammatory properties.OBJECTIVETo evaluate the efficacy and safety of indigo naturalis and its active components in the treatment of psoriasis.METHODSSeven databases were searched for studies of indigo naturalis and its active components for the treatment of psoriasis.RESULTSThe findings demonstrated a higher response rate in the Chinese herbal medicine (CHM) formula groups than in the control group for Psoriasis Area and Severity Index 60 (PASI60) (Rate difference [RD] = 0.22, p < .0001). Among all adverse events, only the incidence of gastrointestinal adverse reactions was higher in the CHM formula group than in the control group (RD = 0.09, p < .0001). In preclinical in vivo studies, indirubin showed better performance in improving the phenotype of psoriasis-like mice compared to that in controls, including the PASI score (mean difference [MD] = -3.58, p < .0001), epidermal thickness (MD = -29.13, p < .0001), interleukin-(IL) 17 A mRNA expression (MD = -2.27, p = .0066) and IL-23 mRNA (MD = -5.36, p = .01).CONCLUSIONIndigo naturalis combined with conventional treatments is useful for treating psoriasis. Indigo naturalis display anti-proliferative, anti-inflammatory and anti-angiogenic effects by regulating the TAK1, JAK3/STAT3, Wnt/β-catenin, Akt/PKB, FAK and AP-1/c-Jun pathway.