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Background: Recent studies have shown that rutin presents a heightened interest due to the plethora of biological activities. The major drawback for this phytocompound is the poor water solubility, a parameter that limits its bioavailability. The study aimed to prepare and assess the inclusion complexes of rutin with β-cyclodextrin (BCD) and hydroxypropyl-β-cyclodextrin (HPBCD), followed by the evaluation of the antioxidant, antiproliferative and pro-apoptotic activity against B164A5 murine melanoma cell line. Methods: Inclusion complexes were prepared by kneading method. Scanning electron microscopy, differential scanning calorimetry and X-ray powder diffraction were used in order to assess their formation. Antioxidant activity was determined by DPPH assay. Antiproliferative and pro-apoptotic effects where tested by MTT, respectively Annexin V-PI assays. Physico-chemical methods proved that incorporation took place. Results: Results show that rutin presents antioxidant activity, and complexation increases this property. After 72 h of incubation at the concentration of 100 µM rutin proved to be an active antiproliferative and pro-apoptotic compound against B164A5 cells. Conclusion: Incorporation in BCD and HBCD maintained the activity, thus representing an important finding and open path for in vivo experiments.