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Background: Spirulina platensis (S. platensis) is a filamentous and photosynthetic microalgae that contains 25 kinds of vitamins and minerals and bioactive compounds such as flavonoids and polyphenols. The aim of this study was to evaluate the antioxidant and cytotoxic activities of ethanolic extract of S. platensis. Materials and Methods: The polyphenolic content, flavonoid content and antioxidant activity of the ethanolic extract of S. platensis was evaluated by Folin-Ciocâlteu reagent, chloride aluminum method, and CUPRAC, respectively. The cytotoxicity of extract on HCT116 and SW742 colorectal cancer cells was determined using an MTT assay after 24, 48 and 72 h treatment with various concentrations of S. platensis extract (0-1000 μg/ml). Results: The ethanolic extract of S. platensis showed an antioxidant activity of 53/7±6/63 mg of Ascorbic acid/g dried sample and was characterized with a high level of polyphenolic and flavonoid content. A dose and time dependent decrease in the viability of HCT116 and SW742 cells was detected following exposure to the extract. After 72 h treatment, IC50 value of HCT116 and SW742 cell lines was obtained as 14/79±0/33 µg/ml and 13/26±1/52 µg/ml, respectively. Conclusion: The results of the present study showed that the ethanolic extract of S. platensis decreases colorectal cancer cell viability significantly. Therefore, this extract can be a candidate for producing anticancer agents. [ABSTRACT FROM AUTHOR]