Every year million tons of by-products and waste from olive and orange processing are produced by agri-food industries, thus triggering environmental and economic problems worldwide. From the perspective of a circular economy model, olive leaves and orange peels can be valorized in valuable products due to the presence of bioactive compounds such as polyphenols exhibiting beneficial effects on human health. The aqueous extracts of olive leaves and orange peels rich in phenolic compounds were prepared by ultrasound-assisted extraction. Both extracts were characterized in terms of yield of extraction, total phenolic content and antioxidant capacity; the polyphenolic profiles were deeper investigated by HPLC-MS analysis. Each extract was included in liposomes composed by a natural phospholipid, 1,2-dioleoyl-sn-glycero-3-phosphocholine,and cholesterol prepared according to the thin-layer evaporation method coupled with a sonication process. The antimicrobial activity of the extracts, free and loaded in liposomes, was investigated according to the broth macrodilution method against different strains of potential bacterial pathogenic species: Staphylococcus aureus (NCIMB 9518), Bacillus subtilis (ATCC 6051) and Enterococcus faecalis (NCIMB 775) as Gram-positive, while Escherichia coli (NCIMB 13302), Pseudomonas aeruginosa (NCIMB 9904) and Klebsiella oxytoca (NCIMB 12259) as Gram-negative. The encapsulation of olive leaves extract in liposomes enhanced its antibacterial activity against S. aureus by an order of magnitude.