Smoothies may represent an excellent way to increase fruits and vegetables consumption as well as their diversity, resulting in an intake of a broader range of natural bioactive compounds, including (poly)phenols. This research aimed to design novel fruit and vegetable-based smoothies with an improved (poly)phenolic profile, based on the content and complementarity of these bioactive compounds among plant ingredients. First, an in-depth and accurate LC-MS/MS analysis targeting characteristic (poly)phenols of each matrix allowed to select promising ingredients for incorporation into the smoothie. The LCMS/MS method included 57 (poly)phenols providing high coverage for a wide range of structurally different (poly)phenols and used pure standards, for accurate identification and quantification. The combination of Granny Smith apple and green celery with dried green chicory and peppermint leaves was promising for smoothie formulations and was further assessed based on sensory evaluation. The enrichment of a fruit and vegetable-based product with additional leafy green vegetables excelled to increase the (poly)phenol content and their diversity, resulting in a green smoothie with a high concentration of (poly)phenols (2947.68 ± 5.17 µg/g dm) and encompassing flavan-3-ols, hydroxycinnamic acids, flavanones, flavonols, flavones and dihydrochalcones provided by the selected plant sources. High-Pressure Processing (HPP) was explored as potential non-thermal preservation technology applied to the developed smoothie. Thus, different pressure levels (300-600 MPa) and holding times (2-10 min) were applied to the (poly)phenol-rich smoothie. Response Surface Methodology was used to predict the optimal combination of pressure and holding time to obtain a microbiologically safe beverage without compromising sensory properties and (poly)phenols. The overall desirability function revealed 600 MPa and 6 min as the optimal combination. Our research highlights the effectiveness of pressure-based technologies as preservation tool in fruit and vegetable-based beverages, along with the maintenance of their appreciated characteristics, such as colour or (poly)phenolic compounds. Nevertheless, the application of thermal processing is still the most widely used and costeffective process to extend the shelf-life in food products. Thus, the impact of non-thermal (HPP) and thermal (HTST) preservation technologies applied to the developed smoothie on its (poly)phenols and their release from the food matrix after gastrointestinal digestion, including the action of gut microbiota, was studied. The application of HPP and HTST technologies preserved the (poly)phenolic profile and the content compared to the unprocessed smoothie. Both preservation technologies showed a protective effect against degradation of (poly)phenols along the gastrointestinal tract, among which thermal processing (HTST) led to a better preservation of them with more than 2-fold higher bioaccessibility (44%) compared to the untreated (17%) and HPP-treated (21%) smoothies. Native (poly)phenols were almost completely converted (83-87%) into lowmolecular-weight catabolites by the gut microbiota in untreated and treated smoothies. However, HTST treatment favoured the generation of higher concentrations of gut-related metabolites after 48 h of colonic fermentation compared to untreated and HPP-treated smoothies, as a consequence of the improved bioaccessibility of the major representatives after in vitro gastrointestinal digestion, hydroxycinnamic acids and flavan-3-ols.