The present invention relates to the technical field of medical devices, in particular to a drug coating, a drug-coated balloon and a preparation method thereof. The drug coating comprises a drug active coating and a positively-charged hydrophobic modified layer which are sequentially attached to the surface of a substrate. By providing the positively charged hydrophobic modified layer comprising the positively-charged modified substance and the hydrophobic substance, the entire surface of the drug coating is given positive electric charge and hydrophobic property. Such positive electric charge characteristics make the drug coating can be strongly combined with the negatively-charged inner wall of blood vessels, so that the drug coating can be permanently adsorbed on the inner wall of blood vessels. The combination of positive electric charge characteristics and hydrophobic property can effectively resist the influence of blood flow on the erosion of drug coating during transportation.