Spirulina platensis (S. platensis) is a blue-green microalga that belongs to the cyanobacteria family. The goal of this research was to investigate the anticancer activity of encapsulation Spirulina platensis algae with Chitosan-Alginate polyelectrolyte nanoparticles on HepG-2, Caco-2, and Vero cell lines and profile its chemical components . S.platensis was extracted using 90% MeOH as a crude extract which was fractionated using different organic solvents. While Nanoencapsulation of 90% MeOH ext. and pet-ether fr. by Chitosan-Alginate polyelectrolyte nanoparticles were prepared by modified ionic gelation method. The chemical composition of 90% MeOH ext. was identified using the GC-MS technique. The 90% MeOH ext. of S. platensis showed high toxicity on HepG-2 and Caco-2 cells, more than the pet-ether fraction. While they were safe on Vero normal cells. Furthermore, nanoencapsulation of the 90%MeOH ext. and pet-ether fr. increased the cytotoxicity against HepG-2 and Caco-2 cells. Moreover, The effect of 90%MeOH ext. and pet-ether fr. NPs against HepG-2 and Caco-2 resulted in a significant increase in the relative expression of the Caspase-3 enzyme and a decrease in the expression of the TNF-α gene and COX-2 enzyme more than the non-encapsulated form. The GC-MS analysis of the silylated 90 % MeOH ext. revealed the presence of 57 bioactive compounds including, alcohols, terpenes, organic acids, and others.