Objective: to investigate the effect of the different types of solvents (water, ethanoland methanol) and extraction methods (ultrasound and maceration) on P. granatum peels and their antiproliferative activity against colorectal cancer cell line HCT116. Methods: The antiproliferative (determined by Neutral red assay) effect of different extraction methods from Punicagranatum peels was tested on the epithelial ovarian cancer (SKOV-3) cell line. Results: The results obtained revealed that the solvents and the extraction methods had a significant effect against HCT116. For the extraction methods applied, the maceration extraction method showed that it has a better anti-proliferative effect compared to the ultrasound method. In addition, the methanol peels extracted by maceration technique showed the highest antiproliferative activity on the HCT-116 cell lines with an IC50 of 31.94 ± 4.98 μg/ml. Conclusion: This study shows than P.granatum peels extracts have great potential as future natural antitumor and antioxidant agents.