Drynaria quercifolia (Linn.) J. Smith has been used in many herbal folklore medicines in Ganjam - Gajapati districts of Odisha state, India. Study pertains to its toxicity profile was undertaken to establish its use as a safe drug for different ailments. Swiss albino mice and wistar albino rats were used for acute and sub-acute toxicity studies respectively. In acute toxicity model, the mice received a limit dose (2000mg/kg) of methanolic extract and kept under observation for 7 days. In sub acute toxicity studies, rats were treated with daily doses (1 g/kg body weight) of methanolic extract for 28 days. In acute toxicity study, samples did not show any mortality at the dose of 2000mg/kg body weight. Further, there were not any significant marked changes observed in hematological parameters too during sub acute toxicity tests. Methanolic extract (ME) of rhizomes of Drynaria quercifolia was found to be safe as a drug. It was without any toxicity at 2000mg/kg body weight and 1g/kg body weight during acute and sub acute toxicity evaluations respectively.