The ethanolic extract of the whole plant of Sphaeranthus amaranthoides was evaluated for antioxidant activity by various in vitro methods like DPPH decoloration assay, Nitric oxide scavenging assay, hydrogen peroxide, superoxide anion radical scavenging assay and reducing power assay. Ascorbic acid was used as a standard for comparison. The extract was found to scavenge the free radicals in a dose dependent manner. The IC50 was calculated for each in vitro antioxidant assays. The ethanolic extract exhibited poor scavenging effect against hydrogen peroxide radical but better scavenging effect against DPPH, nitric oxide and superoxide anion radical. The in vivo antioxidant activity was evaluated against CCl4 – induced liver toxicity in rats. CCl4 induced in vivo toxicity decreased the level of catalase, SOD, GSH, Peroxidase, protein and increased the MDA level in the liver tissue. Treatment with alcoholic extract significantly increased the antioxidant enzymes level and reduced the MDA level in the liver tissue. The present study indicates that the ethanolic extract of Sphaeranthus amaranthoides possesses strong antioxidant activity which supports that the whole plant can be used as an alternate source for the Ayurvedic drug, Munditika for which the accepted source is Sphaeranthus indicus.