The páramo ecosystem is situated in northwest of South America, and it is well known for distribution of lichens. It is documented that lichens produce antioxidant activity, and protect cells from oxidative stress by scavenging free radical. Hence we checked the antioxidant and protective abilities to prevent cell and DNA damage by oxidative stress of Lobariella pallida and Stereocaulon strictum var. compressum extracts. Additionally, the active constituents namely lobariellin (1), methyl orsellinate (2), stereocaullin (3), methyl haematommate (4), methyl β-orcinol carboxylate (5), porphyrilic acid (6) and atranorin (7), were isolated from both extracts and their antioxidant activity was evaluated. The DPPH·, ferric reducing power and inhibition of lipid peroxidation model were used to determined the antioxidant activity of extracts and isolated compounds. The cell and DNA protective effects of extracts and isolated compounds were investigated by exposing keratinocytes, neurons and pUC18 plasmid to hydroxyl radicals, and examined cell viability or DNA cleavage of sample. The findings exhibits that the compounds 1, 4 and 6 scavenged free radicals, inhibited lipid peroxidation and reduced ferric ions at maximum level compared to other isolated compound and extracts. Additionally, 1 and 4 protected cells from oxidative damage and 1 also preserved DNA. These results suggest that 1 and 4 imparts antioxidant activity to prevent oxidative skin and neurodegenerative damage.