OBJECTIVES: Grapefruit juice is known for its ability to interact with the pharmacokinetics of many drugs. This work aims at characterising and synthesizing evidence on this interaction via systematic reviews and modelling.  METHODS: Systematic review was performed to collect data on metabolic interactions between 35 drugs metabolized via the CYP3A4 metabolic pathway and grapefruit juice. Magnitude of interaction was defined as the ratio of areas under the curve with and without grapefruit juice. A Bayesian hierarchical meta-analysis model was used to quantify such interactions and the chemical-specific inter-individual variability. Impact of real-world metabolic interactions on benefit risks on drugs was discussed. RESULTS: Data from more than two hundred studies were collected, involving 35 widely used drugs. Grapefruit juice property to inhibit the CYP3A4 elimination translated into up to 20-fold higher internal doses hence raising potential safety concerns. Statistically significant magnitudes of pharmacokinetic effect ranged from 1.09 to 22.07. The mean magnitude of (CYP3A4-specific) interaction was estimated at 3.73 (95%-credibility interval [0.76-23.14]).  CONCLUSIONS: This work illustrates how real-life food-drug interactions can severely impact real-world benefit/risk of drugs. Such information may be accounted for to inform risk management plans and to optimize early drug development.