Leishmaniasis (both visceral and cutaneous) and Chagas disease (CD) are among the most neglected tropical diseases, with limited treatment options and an urgent need for safer, more effective therapies. DNDI-6148, a benzoxaborole with anti-leishmanial and antichagasic activity, is currently under clinical development. A first-in-human (FIH), Phase 1 study (ISRCTN54981564) has recently assessed the safety, tolerability, and pharmacokinetics of DNDI-6148, demonstrating a good safety profile and, based on non-compartmental analysis, non-linear pharmacokinetics. To support dose selection for future clinical trials, we conducted a population pharmacokinetic analysis using data from the FIH study. The analysis included data from 48 healthy male participants who received a single oral dose of DNDI-6148 (10–380 mg) across eight dosing cohorts. Plasma concentrations were quantified by liquid chromatography–tandem mass spectrometry, and concentration–time data were pooled and analyzed using nonlinear mixed-effects modeling. DNDI-6148 pharmacokinetics were non-linear and best described by a one-compartment disposition model. Higher doses were associated with decreased relative bioavailability and clearance, resulting in less than dose-proportional increases in peak plasma concentrations. The median elimination half-life increased with dose, ranging from 12.6 to 33.7 hours. In summary, the population pharmacokinetic model adequately described DNDI-6148 pharmacokinetics in healthy participants. It provides a valuable tool to guide dose selection for future clinical trials in patients with leishmaniasis and Chagas disease.