The invention belongs to the technical field of medicine and material chemistry, and relates to a chondroitin sulfate-modified natamycin eye drop and a preparation method thereof. The components of the eye drop and its content are: , the content of the added chondroitin oxysulfate-natamycin freeze-dried powder is 10-80 mg, and the preparation method steps include: preparing chondroitin oxysulfate-natamycin granules, preparing chondroitin oxysulfate-natamycin drug granules, preparing eye drops Three process steps, the prepared chondroitin sulfate-natamycin is applied in ophthalmology to prepare eye drops for the treatment of fungal keratitis, the eye drops have strong water solubility, strong corneal penetration, and toxicity Small, anti-fungal, and anti-inflammatory, it directly acts on the ocular surface without releasing and degrading, and has quick effects, promotes the proliferation and migration of corneal epithelial cells, and promotes corneal epithelial repair. The preparation process is simple, easy to operate, and widely used.