Nowadays, the health benefits associated with the consumption of plant-based food constitute a hot topic. To further demonstrate such benefits, related to antioxidant, anti-microbial, and anti-inflammatory activities, as well as the reduction of the risk of several pathophysiological conditions, the study of bioaccessibility and bioavailability of specific food’s constituents, which require interdisciplinary networks, is essential. In this frame, although different experimental models can be developed, the workflow described in the present work support the application of intervention trials in humans as the first option to study the truly effects on health of foods (e.g., plant-based foods), due to the safe condition of them and the realistic approach of this kind of studies, later explored in depth resorting to in vitro, ex vivo, and pre-clinical models, as the most appropriate workflow to get reliable results in the field of Food Science and Nutrition, regarding mechanisms of actions and molecular interactions. Thereby, the work described in the present review is developed in the frame of two consecutive and interconnected projects: BEBESANO (concluded) and MODELSANO (in process) that demonstrate the efficiency of the workflow proposed for research in the Food Science and Nutrition fields. In this regard, in the frame of BEBESANO, acute and longitudinal interventions in humans, devoted to set-up bioavailability of bioactive compounds, followed by functional studies in vivo upon pre-clinical models were conducted to unravel the relationship between bioactive compounds in plant-based beverages and the use of sweetener replacer. Now, most relevant findings from BEBESANO are being further explored in the newly granted project MODELSANO, which is aimed to uncover gaps of knowledge about the mechanisms behind the descriptive results obtained in BEBESANO, using more restrictive in vitro models (allowing the development of studies on the cellular and molecular pathways involved), and integrative cutting edge mathematical modelling alternatives. Keywords: In vivo; in vitro; bioavailability; bioaccessibility; bioactivity; health-promoting foods; metabolomic; mechanistic studies