This study evaluated the acute and sub-chronic toxicities of ethanol leaf extract of Dryopteris filix-mas. Acute toxicity and phytochemical tests on ethanol leaf extract were determined. In sub-chronic toxicity test, animals were treated with 62.5, 125, 250 and 500 mg/kg of extract every day for 90 days. Blood samples were collected via retro-orbital puncture for baseline studies and at 31, 61 and 91st days for determination of hematological, kidney and liver function parameters. Liver and kidneys were harvested for histopathology analyses on 91st day. Also, a 28 day recovery study was carried out to determine reversibility in toxicological effects. Phytochemical screening revealed the presence of tannins, phenols, flavonoids, saponins, steroids, alkaloids, terpenoids, reducing sugar and cardiac glycosides. Acute toxicity test did not show toxicity or death at 5000 mg/kg. There was significant (p<0.005) reduction in white blood cell and lymphocyte counts, significant (p<0.05) increase in some liver and kidney biomarkers as well as alterations in liver and kidney histo-architecture on 91st days in animals that were treated with 250 and 500 mg/kg extract. However, toxicities observed on 91st day were reversible in recovery studies. The leaf extract of Dryopteris filix-mas may be hepatotoxic and nephrotoxic when used for long periods