Umbu (Spondias tuberosa) is a Brazilian Caatinga native fruit that has socioeconomic importance. Pulp is the main product of its agro-industrialization. However, de-pulping gives rise to about 25% residue. It is known that fruit peels and seeds are composed of macro and micronutrients as well as bioactive compounds, offering the umbu residue an opportunity to add value to the fruit agro-chain. As the recovery of bioactive compounds from umbu seeds has not yet been optimized, this work aimed to evaluate their recovery through a more sustainable approach, using propylene glycol as a solvent in microwave-assisted solid–liquid extraction. For that, an experimental design varying the propylene glycol percentage (15–85%) and temperature (59–201 °C) was adopted. The total phenolic compounds (TPC) and antioxidant capacity according to DPPH^• were evaluated as responses. The highest values were found at 201 °C and 50% propylene glycol (3242 mg GAE/100 g and 162 µmol Trolox/g for TPC and DPPH^•, respectively). The values observed were, at least, 8 times higher than those obtained in the worst experimental condition (25% propylene glycol and 80 °C), showing that the independent variables had an effect on the evaluated responses (p < 0.05). All models were significant, displaying p value < 0.05, and no lack of fit was observed. High adjusted R² values (>0.95) confirm the good fit of the data to the models. Thus, microwave-assisted extraction employing propylene glycol as a solvent could be a more sustainable method for the use of umbu seeds.