Acetylcholinesterase, tyrosinase, and α-glucosidase inhibition activities of Euphorbia schimperiana andEuphorbia balsamifera extracts, fractions, and available pure compounds were evaluated for the first time. Acetylcholinesterase assay revealed a significant inhibitory activity of E.balsamifera total extract and n-hexane fraction with 47.7% and 43.3%, respectively, compared tothe reference drug, which was 75%. The n-butanol fraction demonstrated tyrosinase inhibitory activity for E.balsamifera and E.schimperiana with 36.7% and 29.7%, respectively, compared to 60% for the reference drug. Quercetin-3-O-α-glucuronide, quercetin-3-O-β-D-glucuronide-methyl ester, quercetin-3-O-α-L-rhamnoside, 3,3'-di-O-methyl ellagic acid,3,3'-di-O-methyl-ellagic acid-4-β-D-xylopyranoside, and 4-O-ethyl gallic acid were identified from E.schimperiana while quercetin-3-O-glucopyranoside and isoorientin were determined from E.balsamifera. The AChE inhibitory effect ofpure compounds exhibited promising activity, where 4-O-ethylgallic acid demonstrated 51.1%, while the highest tyrosinase inhibition was demonstrated by isoorientin with 50.6% compared to the reference drug (60%). Finally, a molecular docking study was performed for the most promising AChE and tyrosinase inhibitors. The extracts, fractions, and isolated compounds showed no α-glucosidase inhibitory activity.