In order to solve the problem of the poor seed-cleaning performance of the inside-filling pneumatic cotton precision seed-metering device, a double-sided seed-cleaning mechanism combining a seed-cleaning scraper and seed-disturbing air nozzle was designed which can realize alternate seed cleaning on both sides of the suction hole’s end surface. By constructing a mechanical model of the seed-cleaning process, the influence law of the seed-cleaning mechanism on the critical adsorption performance of cotton seed was clarified, and the key structure and parameters of the seed-cleaning mechanism were decided by combining a theoretical analysis with operational requirements. So as to explore the seed-cleaning performance, some relevant bench tests were carried out, with E’kangmian-10 coated de-linted cotton seeds with a moisture content of 8.92% (wet basis) serving as the test objects; and single seed rate, excessive cleaning rate, and missing cleaning rate were taken for test indicators. First of all, a single-factor comparison test was employed with the shape of the seed-cleaning scraper as the impact factor to choose the optimal one. The results of the comparison test showed that, no matter what shape of seed-cleaning scraper was adopted for the seed-metering device, the missing cleaning rates under the corresponding optimal seed-cleaning effect were greater than 5%, and the sharp scraper gave a better seed-cleaning performance than the flat scraper. Next, combining the sharp seed-cleaning scraper with the seed-disturbing air nozzle to form combined seed-cleaning mechanism of the seed-metering device, the Box–Behnken Design test was executed to explore the influence law about seed-cleaning distance, seed-disturbing distance, and seed-disturbing pressure on the seed-cleaning performance. Then the parameter optimization module was applied to achieve the best combination of operating parameters for the test factors. The test results indicated that the test factors influencing test indicators were in the following order: seed-cleaning distance, seed-disturbing pressure, and seed-disturbing distance. The optimal combination of parameters was a seed-cleaning distance of 3.1 mm, seed-disturbing distance of 6.2 mm, and seed-disturbing pressure of 2165 Pa. Lastly, based on the optimal combination, a verification test of seed-cleaning performance was performed, and the corresponding evaluation indexes were a single seed rate of 98.03%, missing cleaning rate of 1.42%, and excessive cleaning rate of 0.55%. In comparison with the optimal seed-cleaning effects under the single-sided seed-cleaning scrapers of flat and sharp shape, respectively, the combined double-sided seed-cleaning mechanism reduced 3.90 and 3.61 percentage points in missing cleaning rate, reduced 2.02 and 1.17 percentage points in excessive cleaning rate, and increased 5.92 and 4.78 percentage points in single seed rate, thus indicating that the combined double-sided seed-cleaning mechanism can effectively enhance the inside-filling pneumatic precision seed-metering device seed-cleaning performance. This study provides a reference for the design and parameter optimization of the seed-cleaning mechanism of a precision seed-metering device.