Inca sayre (Argyrochosma nivea (Poir.) Windham, synonim: Notholaena nivea (Poiret) Desv.) is a Pteridaceae of the Andean region of Peru used in Incan traditional medicine. The aim of this study was to perform the preclinical and clinical evaluation of the hypoglycemic activity of Inca sayre extract in type 2 diabetes mellitus. For this, preclinical evaluation of acute toxicity in mice, and hypoglycemic activity in normoglycemic rats and with experimentally induced diabetes was performed. Clinical evaluation was done in normoglycemic volunteers and type 2 diabetic patients. The results showed hypoglycemic activity of the extract in both preclinical and clinical evaluations. The blood sugar levels in normoglycemic volunteers decreased 11% in comparison to the baseline (p ≤ 0.05). In type 2 diabetic patients reduced 9.0%, 8.2% and 6.2% on the third, fifth and seventh day, respectively, in relation to oral antidiabetics (p ≤ 0.05), and 21.2%, 20.4% and 18.6%, respectively, in relation to placebo (p ≤ 0.05). In addition, the extract produced greater metabolic control of glycaemia in glucose tolerance test (PTOGA).