This study was designed to evaluate the effects of cenobamate, an antiseizure medication for focal seizures, on the pharmacokinetics (PK) of cytochrome P450 probes (bupropion, CYP2B6; midazolam, CYP3A4/5; warfarin, CYP2C9; omeprazole, CYP2C19) in healthy subjects. Probes were administered alone on Days 1 (bupropion) and 7 (midazolam/warfarin/omeprazole), and with cenobamate 100 mg/day on Day 69 (midazolam) and cenobamate 200 mg/day on Days 99 (bupropion) and 105 (midazolam/warfarin/omeprazole). No significant interaction was concluded if 90% CIs for geometric mean ratios (GMRs) for AUC and Cmax of CYP substrates and/or their metabolites were within the no-effect interval (0.80–1.25). When coadministered with cenobamate 100 mg/day, AUC0-tlast GMR (90% CIs) for midazolam was 0.734 (0.647–0.832). When coadministered with cenobamate 200 mg/day, AUC0-tlast GMRs (90% CI) for midazolam, bupropion, S-warfarin, and omeprazole were 0.277 (0.238–0.323), 0.615 (0.522–0.724), 1.14 (1.10–1.18), and 2.07 (1.44–2.98). Coadministration of cenobamate with midazolam and bupropion probes led to values that were outside and below the no effect boundary, indicating that cenobamate induces the CYP3A4/5 and CYP2B6 enzymes. Coadministration of cenobamate led to omeprazole values which were outside and above the no effect boundary, but with much variability, suggesting that cenobamate may moderately inhibit CYP2C19 activity. No effect on CYP2C9 was observed with the cenobamate and warfarin combination. Coadministration of cenobamate with these probes drugs was well tolerated. In this study, 200 mg/day cenobamate moderately induced CYP3A4/5 (dose-dependently; 100 mg/day was a weak inducer), was a weak inducer of CYP2B6, moderately inhibited CYP2C19, and had a negligible effect on CYP2C9.