Olive pomace (OP) is the main residue that results from olive oil production. OP is richin bioactive compounds, including polyphenols, so its use in the treatments of diseases related tooxidative stress, such as cancer, could be considered. The present work aimed to study the biologicalproperties of different OP extracts, obtained by ohmic heating-assisted extraction and conventionalheating, using water and 50% ethanol, in the treatment and prevention of colorectal cancer throughCaco-2 cell models. Additionally, an in-silico analysis was performed to identify the phenolic intestinalabsorption and Caco-2 permeability. The extracts were chemically characterized, and it was found thatthe Ohmic-hydroethanolic (OH-EtOH) extract had the highest antiproliferative effect, probably dueto its higher content of phenolic compounds. The OH-EtOH induced potential modifications in themitochondrial membrane and led to apoptosis by cell cycle arrest in the G1/S phases with activationof p53 and caspase 3 proteins. In addition, this extract protected the intestine against oxidative stress(ROS) caused by H2O2. Therefore, the bioactive compounds present in OP and recovered by applying agreen technology such as ohmic-heating, show promising potential to be used in food, nutraceutical,and biomedical applications, reducing this waste and facilitating the circular economy.