Yellow Fever Virus (YFV) and Chikungunya Virus (CHIV) are neglected reemerging pathogens that cause comorbidities worldwide. Since no antiviral drug is prescribed for those infections, there is a demand on researching compounds that inhibit viral replication. Saponins are amphiphilic compounds that already demonstrated in vitro activity against enveloped virus. Therefore, two purified saponin fractions from Quillaja spp. were evaluated regarding their antiviral potential against YFV and CHIKV. The cell line used in this study was VERO (African green monkey kidney cells) since it is permissive to the replication of both viruses. The antiviral activity of both saponins fractions was screened using the plaque reduction assay protocol. Although saponins did not inhibited YFV replication, they strongly inhibited CHIKV. To confirm the absence of antiviral activity of Quillaja saponins against YFV, the cytopathic effect inhibition assay was performed also. Further studies are required to determine the antiviral mechanisms involved in the CHIKV inhibition.