Abstract The total triterpene fraction isolated from Ganoderma lucidum, a highly nutritional and popular medicinal mushroom occurring in South India, was evaluated for its antioxidant activity in vitro and in vivo. Total triterpenes successfully scavenged DPPH +, ABTS + and superoxide radicals, showed significant ferric reducing activity and was highly effective in reducing the in vitro lipid peroxidation. Activities of the antioxidant enzymes in blood and tissue were increased by the administration of total triterpenes to Swiss albino mice in vivo. The ability of total triterpenes to scavenge the free radicals and to enhance body's antioxidant defence systems indicates its potential use as an antioxidant. An attempt was also done to gauge the toxicity of total triterpenes using acute and sub acute study models in Swiss albino mice. The results showed that Ganoderma triterpenes did not possess significant toxicity. The findings thus reveal the possible therapeutic use of Ganoderma triterpenes.