Psoriasis, a chronic autoimmune disorder, is characterized by keratinocyte hyperproliferation and inflammatory responses. Curcumol, a bioactive terpenoid, possesses antiproliferative and anti-inflammatory properties. This study evaluates the efficacy of curcumol in treating psoriasis in both in vitro and in vivo models. In vitro, curcumol inhibits hyperproliferation and inflammatory responses in a psoriatic HaCaT keratinocyte model stimulated by M5 cytokines by inhibiting the PI3K-Akt pathway. Additionally, in vivo, curcumol ameliorates psoriasis-like skin lesions and inflammatory status in imiquimod-induced mice. Network pharmacology revealed that curcumol's beneficial effects might involve the PI3K-Akt signaling pathway. Further investigation shows that curcumol partially counteracts the activation of PI3K-Akt by recilisib in keratinocytes. These results suggest that curcumol may be a promising therapeutic option for psoriasis.