Whey is an important byproduct of the dairy industry containing mainly lactose and proteins. However, few studies have been conducted on co-utilization of lactose and proteins in whey for chemical production. To establish an efficient bioconversion method for the comprehensive utilization of cheese whey, a low-cost and labor-saving method for D-lactic acid production from cheese whey powder (CWP) was investigated and optimized in this study. CWP could be directly utilized by Lactobacillus bulgaricus CGMCC 1.6970 without the addition of extra nutrients. To fully utilize proteins in CWP, different proteases were selected to hydrolyze CWP, and the highest D-lactic acid concentration was obtained using neutral protease pretreated CPW as substrate. D-Lactic acid concentration could be further improved by adding a small amount of yeast extract. Based on the optimization, 70.70 g/L D-lactic acid with an average productivity of 1.47 g/L/h was obtained from batch fermentation. In fed-batch fermentation, a high D-lactic acid concentration (113.18 g/L) was obtained with an average productivity of 2.36 g/L/h. All the fermentations were carried out under an open condition without sterilization. This study presented a simple and economic strategy for CWP valorization and D-lactic acid production.