This animal experiment was framed to evaluate the beneficial effect of ginsenoside Rg1 (GRg1) against imiquimod (IMQ)-induced psoriasis-like dermatitis model to reveal the underpinning mechanism. Fifty healthy BALB/c mice were divided into five groups as control, GRg1, IMQ induced, oral treatment of GRg1 (50 mg/kg), or dexamethasone (DXM; 10 mg/kg) in IMQ-induced mice. Treatment with GRg1 or DXM significantly mitigates (p < .01) psoriasis area severity index (PASI) score, skin thickness, lipid peroxidation, and inflammatory markers (IL-23, 22, 17A, 1β, and TNF-α). Moreover, administration of GRg1 or DXM considerably reversed the morphological changes induced by IMQ with improved (p < .01) antioxidant activity (SOD, CAT). In addition, a marked downregulation (p < .01) of protein expressions of pIκB and NF-κB p65 (NF-κB signaling pathway) were noted in GRg1 group. Collectively, GRg1 or DXM treatment significantly abolishes IMQ-induced psoriasis-like dermatitis by lowering PASI score, inflammation through downregulating NF-κB signaling pathway. PRACTICAL APPLICATIONS: This is the very first study to explore the efficacy of ginsenoside Rg1 (GRg1) against IMQ-induced psoriasis in the mice model to reveal the underpinning mechanism. The results clearly showed that GRg1 potent anti-psoriasis activity by lowering PASI score, inflammation through downregulating NF-κB signaling pathway. Hence, this study helps in the development of novel nutraceutical/functional food against psoriasis and thus could improve the quality of life in psoriasis patients. However, further clinical trials are needed to justify the above results before developing a commercial functional food using GRg1 against psoriasis.