Spray drying was investigated in this study to produce Moringa leaf powder which was examined for its nutritional value and ability to support probiotics during storage with and without pretreatment. Response surface methodology with central composite rotatable design was performed to optimize the drying process for maximum yield based on two independent variables: inlet air temperature (116–144°C) and feed maltodextrin concentration (8.0%–22.5% w/w). The responding factors include drying characteristics (yield, color, bulk density, tapped density, water activity, and hygroscopicity) and phytochemical content (total phenolic content, total chlorophyll, and antioxidant activity). Each response was fitted to a model with goodness of fit determined using t test, coefficient of determination (R2), coefficient of variation (CV %), lack‐of‐fit, and signal‐to‐noise ratio. Pretreated and non‐pretreated leaves powder at the optimum settings demonstrated viable (more than 106 CFU/g powder) counts of both Lactobacillus acidophilus and Bifidobacterium lactis up to 28 days after inoculation. Practical applications Spray drying is a proven dehydration technique for heat‐sensitive substance in its atomized liquid form to obtain the counterpart dry powder product without substantial thermal degradation. It is a rapid, cost‐effective, and scalable process for the production of dry powders from vegetable and fruits with superior physical attributes and phytochemical properties as compared to other drying methods. Response surface methodology is a statistical tool that is very useful in the optimization and control of food processes. The information provided in this work will serve as the basis for further study on producing spray‐dried Moringa leaves powder at optimal pretreatment and spray drying conditions. The result is very valuable in considering the different processing variables and product qualities at the same time as compared with single factor experiments. This potentially leads to improved product color and phytochemicals retention while increasing production yield. Positive result shown in the probiotic compatible and viability analysis has revealed that the spray‐dried Moringa leaves powder may find its potential applications in the production of probiotic‐fortified Moringa health products (e.g., food, drink, supplements, and so on) and incorporation into existing food products as a flavoring or coloring targeted at the health food sector.