Introduction: A potential new psoriasis therapeutic derived from rhodomyrtone was determined for its safety and efficacy at a psoriasis clinic in a tropical dermatology hospital. Methods: A pilot, open-label trial was conducted in patients with mild to moderate plaque-type psoriasis. A 1% topical formulation was applied to the psoriasis area twice daily for 8 weeks following the initial irritation test. PASI score was assessed at 2, 4, 6, and 8 weeks after intervention. Rhodomyrtone levels in blood plasma were evaluated at 0, 4, and 8 weeks. Haematological analysis and biochemical tests were performed to ensure the safety of the formulation. Results: Initial safety assessment of 1% topical formulation in eight psoriasis patients showed no signs of skin irritation or allergic reaction within 24 hours. Reduction in PASI score to an average of 30% improvement from baseline, maintained through up to 4 months post-treatment, was observed in 6 patients (75%) who received the 1% topical formulation since week 2, with no adverse effects. In the standard treatment group with 5% liquor carbonis detergens and 0.1% betamethasone, three patients (37.5%) showed a reduction in PASI score throughout the clinical study. By week 8, plasma monitoring revealed that five patients had rhodomyrtone levels below the limit of detection (40 ng/ml), while three had trace amounts of rhodomyrtone detected; however, the levels were much lower than those that could exert adverse effects. Liver and kidney function tests were normal in all patients. Discussion and Conclusion: The Potential efficacy and biocompatibility of the 1% topical formulation warrant further investigation in a phase 2 clinical trial to support its future use in psoriasis treatment.