The dipeptidyl peptidase-Ⅳ (DPP-Ⅳ) inhibitory activity and physicochemical properties of yak milk casein hydrolysates produced with alcalase, papain and trypsin were investigated. The effect of hydrolysis periods and different proteases on the DPP-Ⅳ inhibitory activity of yak milk casein hydrolysates was assessed by DPP-Ⅳ inhibitory rate. The physicochemical properties of yak milk casein hydrolysates were evaluated by degree of hydrolysis, trichloroacetic acidnitrogen soluble index (TCA-NSI), solubility and ash content. Results showed that the DPP-Ⅳ inhibitory activity of yak milk casein hydrolysate obtained with papain was significantly higher than that of those obtained with alcalase or trypsin at the same hydrolysis period (P < 0.05). The yak milk casein hydrolysate obtained after 0.50 h hydrolysis with papain displayed the highest DPP-Ⅳ inhibitory activity (with inhibitory rate of (53.95 ± 1.57) %), higher extent of hydrolysis degree, and the lowest ash content. The results suggest that peptides with DPP-Ⅳ inhibitory activity can be generated from yak milk casein. The yak milk casein hydrolysate produced by papain may be used as a functional dairy ingredient to develop functional foods.