This study reports a full characterization of the Sicilian sumac, Rhus coriaria L. This fruit represents a potential source of fiber (33.21 ± 1.02%) and unsaturated fatty acids, being the contents of linoleic and α-linolenic acids, 30.82 ± 1.21% and 1.85 ± 0.07%, respectively. In addition, the content of phenolic and total anthocyanin was 71.69 ± 1.23 mg/g as gallic acid equivalents, and 6.71 ± 0.12 mg/g as cyanidin-3-O-glucoside equivalents, respectively. The high content in mineral elements, consisting mainly of potassium, calcium, magnesium, and phosphorus, followed by aluminum, iron, sodium, boron, and zinc, was detected by inductively coupled plasma mass spectrometry (ICP-MS). Moreover, its antimicrobial activity was evaluated against multidrug resistant (MDR) microorganisms, represented by Escherichia coli and Klebsiella pneumoniae strains isolated from poultry. The activity of seven different sumac fruit extracts obtained using the following solvents—ethanol (SE), methanol (SM), acetone (SA), ethanol and water (SEW), methanol and water (SMW), acetone and water (SAW), water (SW)—was evaluated. The polyphenol profile of SM extract, which showed better activity, was analyzed by ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). The major component identified was gallic acid, followed by quercetin, methyl digallate, pentagalloyl-hexoside, and kaempferol 3-O-glucoside. The non-toxicity of Sicilian R. coriaria was confirmed by testing the effect of the same extract on zebrafish embryos.