Olive oil production yields a substantial volume of by-products, constituting up to 80% of the processed fruits. The olive pomace by-product represents a residue of significant interest due to the diverse bioactive compounds identified in it. However, a thorough characterization and elucidation of the biological activities of olive pomace are imperative to redirect its application for functional food, nutraceutical, and pharmaceutical purposes both for animals and humans. In this review, we examine data from experimental models, including immortalized human vascular endothelial cells, human corneal and conjunctival epithelial cells, human colorectal adenocarcinoma cells, non-tumorigenic human hepatoma cells, and murine macrophages alongside clinical trials. These studies aim to validate the safety, nutritional value, and pharmacological effects of olive pomace. In vitro studies suggest that biophenols extracted from olive pomace possess antioxidant, anti-inflammatory, and antiproliferative properties that could be beneficial in mitigating cardiovascular disorders, particularly atherosclerosis, hepatosteatosis, and dry-eye disease. Protective effects against dry-eye disease were confirmed in a mouse model assay. Olive pomace used in the feed for fish and poultry has demonstrated the ability to enhance animals’ immunity and improve nutritional quality of meat and eggs. Human clinical trials are scarce and have revealed minimal biological changes following the consumption of olive pomace-enriched foods. However, alterations in certain biomarkers tentatively suggest cardioprotective properties. The review underscores the value of olive pomace while addressing potential drawbacks and future perspectives, with a specific focus on the need for further investigation into the animal feed and human nutritional properties of olive pomace. © 2024 Society of Chemical Industry.© 2024 Society of Chemical Industry.