The invention discloses a complex cleaning solution as well as a preparation method and application thereof, and belongs to the field of chemical scale removal. The complex cleaning solution comprises the following components in percentage by weight: 10-35 percent of chelating agent, 6-10 percent of pH adjusting agent, 2-5 percent of osmotic stripping co-solvent and the balance of water; the pH of the complex cleaning solution is 10-13. The chelating agent is a glutamic acid-N, N-tetrasodium diacetateaqueous solution with a solid content of 45-50 percent and/or a hydroxyethyl ethylenediamine acetate trisodium aqueous solution with a solid content of 38-45 percent. The dissolution of calcium sulfate scales is promoted through the pH adjusting agent and clear water, so that calcium ions in calcium sulfate and the chelating agent generate a stable water-soluble internal complex under the action of chelating adsorption to remove the calcium sulfate scales in a water injection channel. Through the osmotic stripping co-solvent, the surface tension of the complex cleaning solution is reduced, and the chelating reaction is promoted. With the adoption of the degradable chelating agent, the complex cleaning solution is more environment-friendly. The complex cleaning solution disclosed by the invention is high in calcium sulfate scale removal rate, safe and environment-friendly, simple and convenient to use, and convenient for large-scale popularization and application.