Skin cancer is a progressive disease which causes degradation of ECM components that leads to inflammation of skin, formation of wrinkles, epidermal hyperplasia and disturbances in the dermal collagen and elastin bundles. Exposure of UV radiation causes release of various enzymes and chemicals mediators which acts as a marker in the detection of cellular degeneration. MMP-1 and TNF-α are markers of cell damage by UV irradiation. Since skin cancer hampers the normal cellular functions, the property of the skin to rejuvenate and replenish itself gets destroyed. We, in our study have put forward an approach to treat the UV radiation caused skin cancer naturally by formulating novel vesicular cream of Aloe vera. The novel vesicle selected was ethosomes because of their good skin penetration property. Aloe vera is used as the phytosources because of its proven ability in treating skin complications. Through our study we have tried to prove the successful encapsulating efficacy of ethosomes particularly for herbal extracts and its skin targeting potentials. Aloe vera extract incorporated ethosomes were developed as cream formulations whose efficacy was established through different skin parameters in vitro and in vivo.