Pomelo fruit is naturally rich in health-promoting components. However, few studies have quantified phytic acid (PA), which is both an antioxidant compound and an antinutrient that limits mineral bioavailability. In this study, we analyzed the temporospatial changes in fruit PA, total phenolic, total flavonoid, estimated mineral bioavailabilities, and their response to fertilization strategies. Compared to pulp, pomelo peel contained higher PA, total phenolic, total flavonoid and most minerals concentrations (except for P) but lower estimated mineral bioavailabilities (Mg, Zn and Fe). The concentrations of PA, total flavonoid, and minerals (P, Ca, Mg, Zn) and Fe estimated bioavailability in pulp gradually decreased with ripening. Total phenolic concentrations and the estimated bioavailabilities of Ca, Mg and Zn in pulp decreased in the early fruit expansion stage but subsequently increased markedly until maturity. Reduced chemical fertilization while supplementing Mg simultaneously increased estimated mineral bioavailabilities in pulp through reduced PA as an antinutrient, and increased bioactives concentrations in peel through increased PA as an antioxidant together with total phenolic and total flavonoid. Overall, our results indicate that reducing NPK while supplementing Mg fertilization in pomelo orchards with acidic and Mg-deficient soil is the most beneficial approach for achieving biofortification of the edible pulp parts and integrated fruit quality enhancement.