Bacopa monnieri (L) Wettst. (B. monnieri) and five major phytoconstituents have been beneficial for neuropharmacological disorders treatment. Herb-drugs interaction (HDIs) could occur due to inhibition or induction of drug metabolism enzymes. It could alter the pharmacokinetics and resulting therapeutic failure. Currently, there have been reported that B. monnieri extract (BME) could inhibit drug-metabolizing enzymes using recombinant Cytochrome P450 (rCYPs). However, no study related to the induction effect of the BME using HepG2 cells has been conducted. To achieve this purpose, the induction effect of the BME, as well as five major constituents on six major CYP isoforms, were analyzed using HepG2 cells. The non-cytotoxicity assay at 120 µg/mL of BME was selected to test the potential of BME to interact with the hepatic cytochrome P450 system. As the results of qRT-PCR, BME, bacoside A₃, and bacopaside II could significantly increase the CYP1A2, 2B6, and 3A4 activities and mRNA expression. Besides, bacopaside A₃ and bacopaside II might be the major phytoconstituents that drive the induction effect on CYP1A2, 2B6, and 3A4 in HepG2 cells. Until more data are available for BME, people taking simultaneously medications and BME are advised to exercise with caution since it cannot conclude from the present study whether BME could cause herb-drug or herb-herb interactions in humans, especially through lower CYP1A2, 2B6, and 3A4 activity.