The Quality-by-Design (QbD) approach was employed to investigate the fluid-bed coating process for the conversion of ginkgo lactone (GL) liquid nanosuspensions into dried nanosuspensions. The effects of critical process variables including inlet air temperature, inlet air capacity and atomizing air pressure were investigated. The particle size and percent yield were optimized using a full factorial design. A Box-Behnken design (BBD) was employed to generate the response surface and optimize process conditions. Multi-linear regression and one-way ANOVA were used to analyze the relationship between critical variables and responses. The results showed that all three selected variables were significant factors (p < 0.05) affecting the particle size. Higher inlet temperature, inlet air capacity or atomizing air pressure will cause an increase of particle size. In addition, the percent yield primarily depended on the inlet air temperature and inlet air capacity (p < 0.05). A higher percent yield was obtained at a higher inlet air temperature or inlet air capacity. The optimal conditions for BBD, including inlet air temperature, inlet air capacity and atomizing air pressure, were set at 40 °C, 11.6 Nm³ and 0.7 bar, respectively. Compared with the raw GLs, the optimized products presented an amorphous state and possessed much faster dissolution. The particle size, percent yield, PDI, zeta-potential and redispersibility index of the optimized products were 254.3 ± 9.8 nm, 82.36 ± 1.87%, 0.155 ± 0.02, −32.9 ± 3.8 mV and 113 ± 4.4% (n = 3), respectively. These results indicate that fluid-bed coating technology based on a QbD approach was sufficient for the solidification of nanosuspensions.