Artesunate, a semi-synthetic derivative of artemisinin, is an anti-malarial agent, currently researched for its anti-cancer properties [1]. The cytotoxic properties of the derivative have been proved superior than those of artemisinin, most likely due to artesunate’s improved solubility [2]. Since cyclodextrins are known compounds used not only to enhance the solubility of a pharmaceutical ingredient, but also the selectivity of an anti-cancer agent against tumor cells [3], in the present study, we focused our attention on a series on inclusion complexes formed between artesunate and Randomly methylated-β-cyclodextrin, Heptakis(2,6-di-O-methyl)-β-cyclodextrin and Heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin. As analytical techniques, thermogravimetry, derivative thermogravimetry, Heat Flow and Fourier transform infrared spectroscopy were employed in order to verify the formation of the guest-host inclusion complexes. Also, as to determine the suitable arrangements of artesunate in the cavity of the selected cyclodextrins, molecular docking for the encapsulation systems was carried out. The cytotoxic activity manifested by the pure substance and the prepared inclusion complexes was evaluated on a melanoma cell line (A375) and on healthy HaCaT keratinocytes.