In this study, thirteen different runs according to the central composite design-response surface methodology were used to optimize the quality parameters of spray-dried bayberry juice powder. The independent variables were different levels of inlet air temperature (145.8-174.1 °C) and maltodextrin concentration (22.9-37.0%). The responses were process yield, moisture content, hygroscopicity, glass transition temperature (Tg), total color difference (ΔE), redness, retention of phenolics and anthocyanins, and antioxidant capacity. The optimum operation conditions for the highest Tg, redness, anthocyanins retention and antioxidant capacity with the lowest ΔE and hygroscopicity were obtained at inlet drying temperature of 150 °C and maltodextrin concentration of 31%. This study revealed that by applying these optimal conditions, bayberry juice powder with a 74.16% yield, 3.15% moisture content, 10.25% hygroscopicity, 41.15 °C Tg, 24.74 ΔE, 27.45 Hunter redness, 89.55% anthocyanins retention, 77.71% phenolics retention, and 30.19 mmol Trolox equivalents/g antioxidant capacity was produced.