By-products of tomato processing are rich in bioactive compounds and their recovery might bring significant economic and environmental benefits. High-pressure homogenization (HPH) (1-10 passes at 100 MPa) was used as a disruption method to recover valuable compounds from tomato peels, using solely water as process medium. Micronization of tomato peels suspensions by HPH reduced their size distribution below the visual detection limit, because of the complete disruption of individual plant cells. With respect to high-shear mixing (5 min at 20000 rpm), HPH processing (10 passes) caused an increased release of intracellular compounds, such as proteins ( + 70.5%), and polyphenols ( + 32.2%) with a corresponding increase in antioxidant activity ( + 23.3%) and reduction in oil-water interfacial tension (-15.0%). Remarkably, also the release of water-insoluble lycopene in the aqueous supematant increased, enabling the recovery of up to 56.1% of the initial peel content, well above what reported in the literature when using organic solvents or supercritical CO2.