An unmet need for patient friendly products can be achieved with novel, biocompatible lipidic formulations which encapsulate and prolong release of medicaments. The aim of this study was to develop a commercially scalable resveratrol-loaded solid-lipid microparticulate (SLM) topical gel for melanoma chemoprevention. Preformulation studies were conducted and drug-excipient interactions examined using infra-red spectroscopy and differential scanning calorimetry (DSC). Resveratrol-loaded SLM topical gel was prepared and evaluated by and parameters. Spherical microparticles of 2.98 μm average size were obtained and DSC thermograms provide evidence of trans-resveratrol encapsulation. and drug diffusion studies revealed sustained release profiles. Optimised SLM gel provides optimum antioxidant, tyrosinase inhibition, cytotoxicity in B16F10 melanoma cell line and apoptosis efficacy. studies on C57BL mice exhibit significant tumour reduction. Promising role of trans-resveratrol-loaded SLM topical gel in melanoma chemoprevention is proven.