Mulberry perishes easily due to its high water content and thin skin. It is important to extend the shelf life of mulberry by proper processing methods. In the present study, the influence of three drying techniques, including hot air drying (HAD), vacuum drying (VD), and vacuum freeze-drying (VFD) on the quality maintenance of mulberry was comprehensively evaluated. Bioactive compounds, antioxidant activity, and the sensory and volatile flavor compounds of mulberry have been researched. The results showed that VFD treatment maintained the highest anthocyanins (6.99 mg/g), total flavones (3.18 mg/g), and soluble sugars (2.94 mg/g), and exhibited the best DPPH· (81.2%) and ABTS⁺· (79.9%) scavenging ability. Mulberry also presented the lowest hardness and the greatest brittleness after VFD. Additionally, VFD maintained the optimal color and presented the best sensory attributes. Furthermore, 30, 20, and 32 kinds of volatile flavor compounds were detected in HAD, VD, and VFD, respectively, among which aldehydes, esters, and ketones were the most abundant compounds. This study indicated the potential application value of VFD for the drying of fruit and vegetable foodstuffs.