Melanoma is the main cause of death from skin cancer. The current treatment methods have prominent toxic side effects. In order to more effectively inhibit melanoma and reduce the toxic side effects during treatment, this paper constructs an engineering system using DSPE-PEG2000-pYEEIE(pYEEIE) molecules to modify exosome-like nanovesicles vesicles of Rhodiola rosea (RELNs) and load Doxorubicin (DOX). As a drug system, the aim is to achieve better targeting activity of the system towards melanoma cell A375. The results showed that the morphology and particle size of the prepared RELNs met the defined criteria for evaluating extracellular vesicles. The pYEEIE-RELNs-DOX drug delivery system has a better inhibitory effect on cell proliferation compared to DOX and RELNs-DOX. At the same time, the pYEEIE-RELN-DOX drug delivery system also showed better targeting towards tumor cells. In summary, this study proposes for the first time RELNs as a new generation of drug delivery carriers and uses them for drug delivery and inhibition of melanoma cell toxicity. This lays the foundation for subsequent animal and clinical experiments, and provides new ideas for the treatment of skin cancer caused by melanoma.