Lemon peel is a by-product rich in phenolic compounds, mainly flavonoids, that provide health benefits to the human’s diet. Quickly, efficiently, and selectively extraction, with the lowest possible cost and environmental impact, is needed to explore the potential of this raw material. For this purpose, the coupling of techniques such as pressurized liquid extraction (PLE) and solid-phase extraction (SPE) has effectively obtained more concentrated extract fractions. Therefore, this work aimed to evaluate the coupling of PLE with SPE for the simultaneous extraction and separation of phenolic compounds from lemon peel, focusing on the use of green solvents. The PLE-SPE variables tested were the type of adsorbent used in the SPE (Sepra™ C18-E, Sepra™ NH2, and PoraPak Rxn), the extract-elution organic solvent combination (water-ethanol and water-ethyl lactate), temperature (40-80 ºC), and pH of the extraction water (4.0, 6.0, and 7.0). The highest yield and separation were observed with the Sepra™ C18-E, using water and ethanol as solvents. Higher temperatures achieved higher yields, mainly of hesperidin and total flavonoids, but negatively affected the adsorbent retention capacity, leading to lower selectivity in separating compounds in the fractions. Using more acidic extraction water, either with pH 4.0 or 6.0, improved the yield of most compounds evaluated. However, it did not improve the retention of flavonoids by the adsorbent at high temperatures. Thus, the developed PLE-SPE method allowed to obtain higher recoveries of most compounds, mainly the total flavonoids (19.82 ± 0.01 mg/g) and hesperidin (12.24 ± 0.01 mg/g) compared to other conventional extraction methods, in addition to separating them into fractions with distinct chemical composition, and also with an environmentally friendly feature. The recovered concentrated fractions have potential applications in food formulations and nutraceutical and drug elaborating.