Date palm by-products are a rich source of bioactive compounds used as antimicrobial agents against common foodborne pathogenic bacteria. which represent a promising option within the modern trend toward natural and safe solutions in food and pharmaceutical applications. The date palm (Phoenix dactylifera L.) seeds showed a significant advantage over leaves in their bioactive compounds. The total phenols reached 3856.67 ± 15.28 mg GAE/100 g in seeds, and 1623.33 ± 25.17 mg GAE/100 g in leaves. Similarly, total flavonoids reached 2310.00 ± 20.00 mg RE/100 g in seeds, and 1963.33 ± 90.74 mg RE/100 g in leaves. A low molecular weight protein/peptide fraction (<14.4 kDa) was also isolated from both leaves and seeds using gel filtration on Sephacryl S-200. The seed extracts exhibited the highest inhibition at 100 mg/mL, reaching 34.00 ± 1.00 mm and 38.00 ± 1.00 mm for the extract of the active compounds against Escherichia coli and Salmonella typhimurium, respectively, and 34.33 ± 0.58 mm and 35.00 ± 1.00 mm for the protein/peptide fraction against Staphylococcus aureus and Bacillus cereus, respectively. MIC/MBC results showed that the active compounds were more effective against Gram-positive bacteria (G+) at 12.5/25 mg/mL, whereas the protein/peptide fraction was more active against Gram-negative bacteria (G-) at the same 12.5/25 mg/mL. The synergistic effect also showed that combining the two extracts resulted in a synergistic effect against S. typhimurium, S. aureus, and B. cereus with FICindex values of 0.457 ± 0.017, 0.475 ± 0.077, and 0.315 ± 0.021, respectively, compared to a combined effect against E. coli with a value of 0.587 ± 0.041.