The increasing antimicrobial resistance and recurrence is a major public health concern leading to high rates of morbidity and mortality worldwide. Furthermore, free radicals induced damage led to oxidative diseases such as cancer and diabetes.Therefore, finding safe and effective antimicrobial and antioxidant agents is vital. Pomegranate peel, constituting 60% of the total fruit's weight, is largely disposed despite its known benefits in traditional medicine. The current study aimed to determine the chemical constituents and biological activities of the methanolic extracts of peels of three pomegranate varieties [wild (PPE-1), white (PPE-2), and red (PPE-3)]. Phytochemicals analysis were performed using UV-vis spectrophotometry, gas chromatography-mass spectroscopy (GC-MS), and high-performance liquid chromatography (HPLC). The antioxidant potentials were determined via 2,2-diphenyl-1-picrylhydrazyl scavenging and phosphomolybdate (ABTS) assay and In Vitro antidiabetic activity was assessed by α-amylase inhibition assay. The antibacterial activity was assesed against three most dominant pathogens including E. coli, Staphylococcus aureus and Staphylococcus epidermidis by disc diffusion. The total phenolics, flavonoid, and tannin contents were highest in PPE-1 followed by PPE-2 and PPE-3. Among the polyphenol, chlorogenic acid was found in substantial concentration in all extracts. The GC-MS analysis identified 13 distinct compounds with the notable presence of 5-(hydroxymethyl) furan-2-carbaldehyde. All varieties exhibited significant antioxidants, antibacterial and antidiabetics, but the PPE-1 showed the highest activities. Docking studies revealed that chlorogenic acid was a strong inhibitor of Cyclooxygenase-II (COX-II) indicating anti-inflammatory and anticancerous potential. The study revealed that pomegranate peels have promising biological potentials such as antioxidants, antidiabetic, and antimicrobial, suggesting their role in drug developments.