Bletilla striata is a good source of plant polyphenols which have regulatory functions on melanogenesis. In the present work, to maximise the yields of total polyphenols extracted from B. striata, the effects of Tween-60 concentration, shear speed, shear time, ethanol concentration, temperature, and material-to-solvent ratio on extraction of polyphenols were assayed using the high-shear dispersing emulsification technology (HSDE). The obtained data were analysed using the response surface methodology, which showed that the optimal extraction conditions were as follows: Tween-60 concentration of 2.00%, ethanol concentration of 69%, shear speed of 17,200 rpm, and extraction temperature of 55°C. Under these conditions, the extraction of the total polyphenols from B. striata was 13.79 ± 0.34 mg/g. Furthermore, the anti-melanogenesis activity of the total polyphenols extracted from B. striata was evaluated using α-MSH-induced B16F10 cells. Results showed that the total polyphenols from B. striata could significantly inhibit melanin production. Overall, these results presented the optimal conditions for the extraction of total polyphenols from B. striata, and also revealed the potential anti-melanogenesis values of B. striata polyphenols.