Phenolic compounds have shown to have a high bioactive potential against various pathologies, postulating as an interesting alternative to manage some diseases. In this sense, both Lippia citriodora and Hibiscus sabdariffa are two botanical sources with a demonstrated high bioactive potential, in which their antioxidant capacity stands out. In this work, the optimization of the extraction conditions for the recovery of phytochemicals from L. citriodora leaves and H. sabdariffa calyces has been carried out using Response Surface Methodologies (RSM) considering their total polar compounds measured by HPLC-ESI-TOF/MS and Folin-Ciocalteu assay, and its antioxidant capacity evaluated by Ferric Reducing Antioxidant Power (FRAP) and Trolox Equivalent Antioxidant Capacity (TEAC) assays. The results showed that to maximize the antioxidant capacity in H. sabdariffa, a moderate temperature and high ethanol percentage are needed, while a low temperature and a high percentage of ethanol are needed in L. citriodora. In addition, with the results obtained in the multiple response analysis, it is possible to affirm the importance of this type of analysis to develop functional ingredients, taking into account both total content of phenolic compounds and their bioactivity. Furthermore, as confirmed in this study, these analyses can be extrapolated in different techniques and in different matrices, with phenolic compounds from different families being important to develop new high added value products for food, pharmaceutical or cosmetic industries.