Cupuassu (Theobroma grandiflorum) is an Amazonian fruit with high nutritional value and considerable antioxidant activity mainly due to phenolics and ascorbic acid. To preserve those compounds and their activity, the pulp of cupuassu was spray dried using inulin/maltodextrin mixtures as wall material. The process was optimized using response surface methodology (RSM) based on a central composite design, with inlet temperature (X1), inulin concentration in the wall material (X2) and wall material concentration (X3) as independent variables. Yield, moisture, water activity (aw), hygroscopicity, water solubility index (WSI), and ascorbic acid (AA) and phenolic (PC) encapsulation efficiency were studied. The fitted results (mostly second-order equations) enabled us to determine the optimal conditions of inlet temperature (185 °C), inulin concentration (44%), and wall material concentration (35%) with low predictive error and high desirability (close to 1.0). The microencapsulates with a sphere of diameter 2.16 ± 1.32 μm had a smooth surface and a low degree of agglomeration. Under simulated intestinal fluid conditions, 76.7% of ascorbic acid was released. These results suggest the great potential of the obtained cupuassu microencapsulates as a strategy for Amazonian fruit valorization.