Cannabis sativa and Curcuma longa have traditionally been used for the management of skin disorders; however, scientific evidence supporting their combined topical use in eczema and psoriasis remains limited. To characterize the phytochemical composition, evaluate the biological activities, investigate potential molecular mechanisms, and assess the preliminary clinical performance of a topical herbal cream containing C. sativa and C. longa extracts. Ethanolic extracts were analyzed using UHPLC and GC-MS. Antioxidant, antibacterial, cytotoxicity, and nitric oxide inhibition assays were performed. Molecular docking studies were conducted against inflammation-related protein targets. A pilot clinical study evaluated the effects of the herbal cream in patients with eczema and psoriasis over four weeks using EASI, PASI, and DLQI scores. The herbal formulation contained cannabinoids, terpenoids, and curcuminoids with measurable antioxidant activity. The extract exhibited low cytotoxicity and moderate inhibition of nitric oxide production in LPS-stimulated macrophages. Docking analyses suggested favorable interactions between selected phytochemicals and inflammation-associated targets. Preliminary clinical observations indicated improvements in EASI, PASI, and DLQI scores among study completers. The herbal cream demonstrated antioxidant and anti-inflammatory properties and showed preliminary clinical potential in inflammatory skin disorders. Larger controlled clinical studies are required to confirm efficacy and establish therapeutic value.