Echinops spinosus, belonging to Asteraceae family, is used in folk medicine as an abortifacient and diuretic and for blood circulation, diabetes, stomach pain, indigestion and spasmolytic problems. The objective of this work is the study of acute toxicity, the content of phenolic compounds (polyphenols, flavonoids and tannins), antioxidant activity (DPPH, ABTS, FRAP, H2O2 and xanthine oxidase) and antidiabetic (α-amylase, α-glucosidase and lipase) in vitro and ex-vivo by studying the starch tolerance test. The phytochemical assay showed that the ethanolic extract is the richest in polyphenols, flavonoids and tannins with 77.01 mg GEA/g extract; 544.33 mg RE/g extract, and 32.20 mg EC/g extract, respectively. The ethanolic extract showed better antioxidant activity compared to the aqueous extract with (IC50=13±0.25 µg/mL; IC50=75.11±0.34 mg TE/g extract; IC50=51.1±1.2 mg AAE/g extract; IC50=28.2±2.87 µg/mL and 16.83 ± 0.72 µg/mL) in DPPH, ABTS, FRAP, H2O2 and xanthine oxidase. Extracts of E. spinosus have shown a remarkable inhibitory effect α-amylase and interesting inhibitory effect of α-glucosidase and lipase. The aqueous and ethanolic extract also lowered blood sugar levels to 0.96 and 0.93g/L, respectively, after 90 minutes in starch-loaded rats. Acute toxicity results indicate that E. spinosus extracts are non-toxic with an LD50 greater than 2 g/kg in female Swiss mice. Therefore, the antioxidant and antidiabetic activity may be at the origin of the bioactive compounds contained in the plant E. spinosus. However, in vivo studies on the mechanism of action are needed against oxidative stress associated with diabetes.