Psoriasis is usually treated with local and systemic medications that have varying degrees of efficacy and safety profiles. We investigated the efficacy and safety of an alternative treatment from natural sources, Mahonia aquifolium, for the management of mild to moderate psoriasis. Two hundred subjects participated in a randomized, double-blind, placebo-controlled study using either the topical cream Reliéva (a homeopathic product containing a proprietary M. aquifolium extract) or control (placebo) twice a day for 12 weeks. Efficacy and safety were assessed using the Psoriasis Area Severity Index (PASI) and the Quality of Life Index (QLI) questionnaires at different times throughout the 12-week study. The PASI was evaluated by the physician at the beginning (week 0) and end (week 12) of the study. The QLI was assessed by patients at weeks 0, 4, 8, and 12. The results indicate statistically significant (P < 0.05) improvements in PASI and QLI in the Mahonia-treated group, compared with the control group. The side effects reported were infrequent, < 1% and minor; the most frequent side effects were rash, a burning sensation when applying the cream, and clothing stain. These data indicate that Reliéva, a proprietary form of M. aquifolium, is effective and well tolerated in patients with mild to moderate psoriasis.