Clofazimine is an emerging drug for the treatment of cryptosporidiosis in infants. As a poorly water-soluble drug, the formulation of clofazimine in age-appropriate vehicles is challenging and often results in the use of off-label formulations. Milk-based vehicles such as human milk and bovine milk have been investigated as age-appropriate formulations and shown to increase the solubilisation of poorly water-soluble drugs via enhanced solubility in lipid digestion products in vitro. We hypothesised that administration of clofazimine within a milk-based vehicle would enhance bioavailability for infant patients. Towards this objective, suspensions of clofazimine in human and bovine milk were orally administered separately to piglets and rats and the subsequent plasma concentrations were compared to those after administration of an aqueous drug suspension. Initial investigations with a rodent model showed a significant increase (258%) in the oral bioavailability of clofazimine when administered with human milk. Similarly, the oral bioavailability of clofazimine was significantly higher when administered in both human (154%) and bovine milk (175%) using a neonatal piglet model, suggesting comparable enhancement in oral bioavailability could be achieved with human or bovine milk. These findings demonstrate the potential of human milk in particular to provide an effective administration vehicle for clofazimine administration to infants without the need for additional excipients.