The present study aimed to investigate Sumac (Rhus coriaria) for anticancer, antidiabetic, anticholinergic activities and total phenolic and flavonoid contents. Two solvents, water and ethanol, were used for extraction. For anticancer activity, the extracts were tested against human cancer cell lines including HT-29 and MCF-7. The cell growth inhibition rate was measured via XTT assay. The antidiabetic activity of the sumac extracts was measured by the inhibition of -glycosidase and -amylase enzymes, whereas the anticholinergic activity was measured via the inhibition of acetylcholinesterase and butyrylcholinesterase enzymes. The total phenolic and flavonoid contents were determined using the Folin-Ciocalteau and the aluminum chloride colorimetric methods, respectively. Liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method was used for the separation, identification and quantification of phenolic compounds in the samples. The ethanolic extract had higher phenolic and phenolic contents than aqueous extract. It exhibited substantial antiproliferative, antidiabetic and anticholinergic activities. The aqueous extract of sumac showed moderate therapeutic efficiency in all the preformed assays. LC-MS/MS study revealed fumaric acid as a main compound in both the ethanolic (452.78mg/kg) and aqueous (180.72mg/kg) extracts. These results suggest that sumac may have health-enhancing effects and act as inhibitors of certain enzymes or interfering with some cellular pathways.