Pradigastat, a novel diacylglycerol acyltransferase-1 inhibitor, was evaluated for both pharmacokinetic (PK) and pharmacodynamic (PD) drug–drug interactions when co-administered with digoxin or warfarin in healthy subjects. This open-label study included two parallel subject cohorts each with three sequential treatment periods. Forty subjects were enrolled in the study with 20 subjects allocated to each cohort. PK and PD (PT/INR for warfarin only) samples were collected in each period. The statistical analysis results showed that the 90% CIs of the geometric mean ratios of digoxin, R-warfarin, and S-warfarin PK parameters (AUC and Cmax) were all within 0.80–1.25 interval. The 90% CIs of the geometric mean ratios of pradigastat PK parameters (AUC and Cmax) were within 0.80–1.25 interval when co-administered with warfarin; while co-administration with digoxin slightly reduced pradigastat exposure (˜15%). The results also showed that 90% CIs of the geometric mean ratios of warfarin PD parameters (AUCPT, PTmax, AUCINR, and INRmax) were within 0.80–1.25 interval. Pradigastat and digoxin or warfarin had no relevant clinical PK or PD drug–drug interactions. Administration of pradigastat and warfarin or pradigastat and digoxin as a mono or combined treatment appears to be safe and tolerated.