Palmatine (PM) is a potent anti-infective agent used to treat eye diseases. However, PM is less effective for ocular application due to short residence time within the eyes. This study aimed to develop a cationic lipid emulsions (CLEs) for ophthalmic delivery of PM and evaluate its suitability in infection treatment. PM-loaded CLEs (PM-CLEs) were prepared through emulsifying/high-pressure homogenisation and characterised by particle size, xi potential and morphology. The resulting PM-CLEs possessed a particle size of 192 nm and xi potential of 45 mV around. In vitro release illustrated that PM was released less from CLEs. Corneal bioadhesion test showed that PM-CLEs exhibited an enhanced ocular residence time. Improved anti-infective activity was achieved in the model of fungus-induced keratitis. Furthermore, PM-CLEs demonstrated predominant cellular uptake and internalisation in the corneal epithelial cells. These results provide proof of concept that CLEs are promising bioadhesive carriers for ophthalmic delivery of PM.