Background: Rehmannia glutinosa, commonly known as Dihuang, is a medicinal herb widely used in the formulations of traditional Chinese medicine. Radix or the root of Rehmannia is a vital ingredient used in various oriental medicines such as Jihwangeumja, Saenghyeoryunbuem, and Gyeongokgo. Hence, in the present study, we evaluated the potency of Rehmannia radix (RR) extract to ameliorate psoriasis like in vivo model induced by imiquimod (IMQ). Materials and Methods: Histopathological and histomorphometrical analysis was performed to assess the effect on RR extract against the psoriasis induction. To estimate whether the RR extract pretreatment inhibits the induction of psoriasis, the oxidative stress and antioxidants status were assessed. Further, to prove ameliorative effect of RR extract against psoriasis induction, the levels of inflammatory cytokines were estimated. Immunoblotting analyses of Janus kinase/signal transducer and activator of transcription (JAK/STAT) protein were estimated to confirm the molecular mechanism of RR extract against psoriasis induction. Results: RR extract effectively scavenged the free radicals, increased the antioxidant status, and decreased the inflammatory cytokines induced by IMQ. It also inhibits the expression of phosphorylated JAK/STAT protein, thereby preventing the dermis from inflammation. Histological analysis of psoriasis-induced and RR-pretreated mice' skin tissue authentically proves the inhibitory effect of RR extract against psoriasis induction. Conclusion: Our overall results suggest that RR extracts possess antipsoriatic property and can be subjected to human trial in the future as antipsoriatic drug.