The aim of this work was to encapsulate of citrulline extract from watermelon rind (by-product) by spray drying. Two different pectins were probed as wall materials in addition to maltodextrin. A Box-Behnken design was applied and three different parameters were evaluated as factors: commercial pectin (CP) concentration, orange produced pectin (OPP) concentration, and inlet air temperature. Different powder properties were evaluated as response variables including drying yield and encapsulation efficiency. The spray drying process was optimized by the desirability function. Higher drying yields, moisture contents and encapsulation efficiencies were reached at higher commercial pectin concentration. The optimal spray drying conditions were also determined. The obtained powder at the optimal conditions was characterized using Modulated differential scanning calorimetry and thermogravimetric analysis. In conclusion, citrulline extract spray-dried powders showed that could be stable during storage, so it might be used as an additive in foods to obtain functional products for human consumption.