This study aimed to assess the phytochemical profile and associated functional properties of sumac (
Rhus coriaria L.) fruits harvested from wild plants in Sicily. Chemical characterization unveiled exceptionally high levels of polyphenols (10.99 g GAE/100 g DW), including substantial quantities of proanthocyanidins (61.577 mg PACE/100 g DW), and identified 82 phytochemicals belonging to various flavonoid classes. The hydroalcoholic extract from Sicilian sumac exhibited remarkable redox-active properties, providing antioxidant protection in a cell-based model of lipid peroxidation (CAA50: 1.116 μg/mL). Additionally, it displayed significant antiproliferative activity against four human tumor epithelial cell lines with GI50 values ranging from 31.08 to 149.74 μg/mL and robust antibacterial activity against major foodborne pathogens (MIC: 12.5–25.0 mg/mL). Our findings highlight Sicilian sumac fruit as a rich source of phytochemicals that positively contribute to the cellular redox state even when consumed in small quantities. Additionally, its diverse bioactivities indicate potential applications across food and non-food sectors.