Interest in the biological role of bioactive compounds present in plant by-products has increased over the last few years. This study aimed to investigate the nutritive value and biological activities of Egyptian Grape leaves (GL), Grape seeds (GS) and Mulberry leaves (ML), as well as investigate the impact of γ-irradiation for improving the utilization of these plant byproducts. The dose level 5.0 kGy showed highest the content of crude protein (24.42, 19.41 and 13.50 mg/100 g), as well as crude fiber (34.26 and 21.18 mg/100 g) for ML, GL and GS, respectively. Mulberry leaves has a highest content of protein and fiber at dose 5.0 kGy compared with GL and GS. The highest total phenolic content was found in GS (9.75 mg/g DW), followed by GL (7.32 mg/g DW) and the lowest in ML (5.97 mg/g DW). While ML had a higher total flavonoids content (5.61 mg/g DW) than GS (4.88 mg/g DW) and GL (2.86 mg/g DW). Total phenolic and flavonoid contents were significantly increased at 5.0 kGy. The highest level (83.25% and 80.24%) of scavenging activity (DPPH %) and inhibition activity of HCT 116 cells was recorded at 5.0 kGy by GS. All extracts irradiated at 5.0 kGy exhibited varying degrees of antibacterial activity against (Gram+ve and Gram-ve), the GS followed by GL then ML showed strong antibacterial activity with a diameter of inhibition zone of 26.2, 24.5 and 19.7 mm, against L. monocytoganes, respectively and 24.4, 21.4 and 17.2 against S. typhimurium, respectively. This study suggests that γ-irradiation is an effective technique to enhance the recovery of phenolics and flavonoids from GL, GS and ML. Also in current study, antioxidant, antibacterial and anticancer activity has been suggested to appear a clear positive relationship with the total phenolic material. This study has proved that the Egyptian GL, GS and ML are rich sources of valuable phytochemicals and nutrients that can serve as a potential source of nutraceuticals and multifunctional food additives (antimicrobial, antioxidant, and anticancer). Phenolic compounds recovered from GL, GS and ML may have a potential role in fighting the COVID-19.