Glioblastoma multiforme is a devastating cerebral tumor that submits to an awful prognostic. Because of this, improvements in the treatments are necessary to decrease the side effects and to increase the survival of the patients. Resveratrol, a constituent of the red wine, has been described to inhibit carcinogenesis at multiple stages. Biodegradable nanoparticles are emerging as promissory drug delivery system for specific tissues, and because of its useful uptake by tumor cells. The main aim of the current study was to evaluate the antiproliferative effect of trans-resveratrol-loaded nanocapsules treatment against C6 glioma cell line in culture and in a rat implanted glioma model. Our results showed that trans-resveratrol-loaded nanocapsules decreased the viability/proliferation of glioma cells. This is preceded by an arrest of the cell cycle progression in G2/M and subsequent cell death, represented by sub-G1 phase and propidium iodide stained. In the in vivo glioma model, we observed a significant decrease in the tumor size and reduction in some malignant characteristics, typical of the glioblastomas, in the treated rats with this formulation. These effects were more pronounced with the treatment with transresveratrol- loaded nanocapsules when compared to the treatment with trans-resveratrol in solution. Furthermore, trans-resveratrol-loaded nanocapsules treatment was not toxic to organotypic cultures, a model of healthy neural cells. The present results suggest that this formulation can be a potential useful chemotherapeutic agent for the treatment of brain tumors. More intensive researches are necessary in order to evaluate its clinical feasibility, though.