Spirulina platensis is blue-green algae received significant attention for its high nutritional value, it is a source of powerful antioxidants. The cytotoxicity of crude extract is not well recorded. The aim of current study to evaluate the cytotoxicity of S. platensis extracts on colon cancer (CaCo-2), hepatic cancer (HepG2) cell lines, normal fibroblast cells line (HdFn) and also antioxidant activity. The percent of 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity was determined for serial concentrations of extract ranging from 3.125 to 200 μg/ml. Cell lines were treated for 24 hours with different concentrations of extract ranging from 25 to 400 µg/ml. Cell viability testing using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay which determined how the extract affected caspase 9 activity. The results revealed that extract had moderate antioxidant activity, showing the DPPH scavenging activity reached 58% in a concentration of 200μg/ml, and IC50 was 95.84 μg/ml. The extract significantly decreased CaCo-2 cell viability with IC50 99.12 µg/ml, compared to HdFn viability with IC50 157.6 µg/ml. On CaCo-2 cells, the extract's cytotoxicity was more evident (P< 0.05) than HdFn cells. The extract had more significant (P<0.05) cytotoxicity on cancer cell lines and also significantly decreased the viability of HepG2 cells with IC50 167.4 µg/ml, than the viability of HdFn with IC50 214.9 μg/ml. The extract revealed significantly higher (P< 0.05) cytotoxicity against HepG2 cells than the normal HdFn cells. This study concluded that the extract exerted a dose-dependent anti-proliferation effect on CaCo-2 cells and HepG2 cells by comparing them with HdFn cells.