Lovastatin is a typical drug interacting with grapefruit juice and naringin and vitamin C are main active constituents in fruit juice. It is necessary to study the interaction between lovastatin and digestive enzymes and the effect of naringin and vitamin C on the interaction. Pepsin, trypsin and α-chymotrypsin were selected as representatives of digestive tract enzymes, and fluorescence spectroscopy was employed to study the interaction of lovastatin with three digestive enzymes and the effect of naringin and vitamin C on this interaction. The mechanism of interaction between lovastatin and three digestive enzymes was static quenching. Lovastatin bound to trypsin by electrostatic interaction, while bound to pepsin or α-chymotrypsin mainly by hydrophobic interaction. The conformation of three enzymes changed and non-radiative energy transfer occurred with high probability between three digestive enzymes and lovastatin. Both naringin and vitamin C could reduce the binding stability of lovastatin to pepsin and α-chymotrypsin, increasing concentration of free lovastatin. That is, naringin or vitamin C in the fruit or food may increase the blood concentration of lovastatin; perhaps taking frequency or dosage of lovastatin may be reduced.