In this work, we determined for the first time the Salvia pilifera Montbret & Aucher ex Bentham as an important source for natural products with antioxidant and antidiabetic potentials. In this context, methanol (MESP) and water (WESP) extracts were prepared from aerial parts of S. pilifera. Also, it was evaluated for antioxidant profile by eight distinguishes bioanalytical methods and inhibition effects against enzymes linked to different diseases, namely butyrylcholinesterase (BChE), acetylcholinesterase (AChE), alpha-glycosidase and alpha-amylase. Also, the polyphenolic compositions of MESP and WESP were evaluated by high performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). Fourteen phenolics were identified in the evaporated MESP and thirteen phenolic compounds were identified in the lyophilized WESP. Also, we performed the antioxidant properties of both extracts. In order to estimate the capacity of MESP and WESP to act as antioxidants, 1,1-diphenyl-2-picryl-hydrazyl radicals (DPPH center dot), 2,2 '-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radicals (ABTS(center dot+)) and N,N-dimethyl-p-phenylenediamine radicals (DMPD center dot+), scavenging activities, ferric ions (Fe3+), Fe3+-TPTZ and cupric ions (Cu2+) reducing assays were studied. MESP and WESP were found as potent effective DPPH center dot (IC50: 7.05 and 8.56 mu g/mL), ABTS(center dot+) (IC50: 3.52 and 4.76 mu g/mL) and DMPD center dot+ (IC50: 28.92 and 30.95 mu g/mL) scavenging effects. On the other hand, MESP and WESP showed the potent inhibition effects against AChE (IC50: 94.93 and 138.61 mu g/mL), BChE (IC50: 60.05 and 99.13 mu g/mL), alpha-glycosidase (IC50: 23.28 and 36.47 mu g/mL) and alpha-amylase (IC50: 46.21 and 97.67 mu g/mL) enzymes. This study will be an innovative and guider for further studies for antioxidant properties for industrial or medicinal plants.