Natural deep eutectic solvents (NADESs) have been postulated as alternative green solvents for the isolation of valuable bioactive compounds from Lippia citriodora. Thus, 11 different NADESs, based on choline chloride (ChCl) as the hydrogen bond acceptor in combination with different hydrogen bond donors (organic acids, polyalcohols, sugars, and urea) were tested. According to the results obtained, ChCl-lactic acid exhibited the highest extraction yield for iridoids, 7.25 mg g⁻¹, phenylpropanoids, 17.23 mg g⁻¹, and flavonoids, 9.02 mg g⁻¹ being significantly greater than phenylpropanoid and flavonoid yields, 15.63 and 5.43 mg g⁻¹ respectively, extracted with methanol as conventional solvent. Subsequently, in order to optimise the most influential microwave assisted extraction (MAE) parameters, a Box-Behnken design paired with a response surface methodology were implemented. Temperature and water content showed a strong effect on the extraction of polyphenol sub-classes, while the effect of irradiation time was less noticeable on extraction yields. Temperature of 63.68 °C, a water content of 32.19% and a microwave irrdiation time of 17.08 min were the optimum conditions provided by the statistical program. The use of NADESs showed potential to facilitate the design and customisation of green tailor-made solvents which have greater extraction capacity than conventional organic solvents.