The aqueous-acetone polyphenolic extract of the traditionally derived date syrup, known as "Rub El Tamer", was analyzed using RP-HPLC-DAD and ESI-MS. The phenolic content of the extract was 394.53 ± 1.13 mg per 100 g of syrup with caffeoylsinapylquinic acid as the most abundant compound (72.23%). The extract exhibited strong antioxidant activities as evaluated using the ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)), DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) methods. The extract antimicrobial potential against a range of microorganism strains showed that Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus cereus were the most sensitive bacteria with MBC in the range of 0.5-0.05 mg/mL. Furthermore, in the presence of the syrup extract (8.18-131 μg/mL), the Human SH-SY5Y neuroblastoma and the 3T3 fibroblast cell lines showed dissimilar reduction of viability suggesting a higher cytotoxic effect against tumorigenic cells. Our results provide new insights into date syrup characterization which should stimulate further studies of this hot desert resource.