Mulberry is rich in polyphenols with characteristics of nutritional qualities and bioactive phytonutrients. However, the capacity and health benefit potential are limited due to their weak stability during processing and preservation. Spray drying encapsulation was well-established and widely utilized for protecting bioactive substances such as polyphenols. However, undesirable phenomena such as stickiness on the drier chamber wall arose during spray drying of sugar-rich solution such as fruit juice. Furthermore, powder recovery was decreased owing to stickiness issue during spray drying. Therefore, effect of different total solid ratios of whey protein isolate (WPI) and maltodextrin (MD) in the feed solution on physical and chemical properties of spray dried mulberry juice powders was investigated. The results showed that the powder recovery of spray dried mulberry juice powders was significantly increased when MD in the feed solution was replaced by small amount of WPI. The reason can be attributed to the high surface activity and excellent film-forming properties of WPI. The moisture content of spray dried mulberry juice powders was increased with the increase of WPI mass fraction in the feed solution. However, water activity, bulk density, particle size, water solubility index and glass transition temperature were decreased with the increase of WPI mass fraction in the feed solution. The hygroscopicity of mulberry juice powders was not significantly influenced by WPI/MD ratio in the feed solution. The color parameters of spray dried mulberry juice powders such as L, b and ΔE were increased with the increase of WPI mass fraction in the feed solution. Whereas, opposite behavior was observed for parameter a. The total phenol content and DPPH scavenging capacity of spray dried mulberry juice powders were decreased with the increase of WPI mass fraction in the feed solution.