Background The use of natural preservatives became of great interest; good examples of these natural preservation agents are plant peels. The use of plant peels has dual benefits; first is their antimicrobial activity against food-borne pathogens, while the second is minimizing agro-industrial wastes. Results The evaluation of the antimicrobial potential of both methanolic and ethanolic extracts of three fruit peels (orange, pomegranate, and banana), against 4 Gram-positive (G+), 3 Gram-negative bacteria (G−), and 2 fungal strains revealed that both pomegranate peel extracts exhibited significantly higher inhibitory effect on all tested G+ bacteria. Methanolic extract of pomegranate peel gave higher activity than the ethanolic one against G+ and G− bacteria except for S. typhimurium. Against A. flavus and A. niger, both pomegranate and orange extracts showed activity ranging between 65 and 100% more than the positive control. The ethanolic extracts of all tested peels showed a considerable capacity of antioxidant compounds compared to the methanolic extracts. The highest antioxidant capacity was found for ethanolic and methanolic extracts of pomegranate, 66.870 and 56.262 mg/ml, respectively. Generally, the concentration of total phenolic compounds was higher than that of total flavonoids followed by tannins. The highest readings of all tested constituents were reported for pomegranate extracts followed by orange and then banana. The total phenolic content, total flavonoids, and tannins were proportional to antioxidant values. GC-MS of pomegranate peel extracts identified 23 compounds in the methanolic extract versus 31 compounds in the ethanolic one. These components were identified based on their retention times and mass spectral fragmentation pattern. 5-hydroxymethylfufural (HMF) represented the major component in both methanolic and ethanolic extracts with peak area percentage of 65.78% and 48.43%, respectively. Conclusions The results showed negative effect of methanolic and ethanolic extracts of pomegranate on G+ and G− bacteria and two fungal pathogenic strains. The phytochemical analysis regarded these results to the high content of phenols, flavonoids, and tannins. GC-MS chromatogram identified many compounds known to be effective as antioxidants and antibacterial and antifungal agents. These indications show that pomegranate peel may be a superior natural food-preserver, but further studies about the suitable formulation, dosage, and possible side-effects are still needed.