Tannins are a class of phenolic compounds commonly found in plants and studied for their bioactive and
inhibitory enzyme properties. Cytinus hypocistis (L.) L. is a wild edible parasitic plant whose biological properties
have been correlated with its high tannin content. Thus, studying the extraction of tannins from C. hypocistis will
give comprehensive clues to enhance the recovery of these high added-value bioactive compounds. The present
work applied Response Surface Methodology (RSM) to optimise tannins extraction using Heat-Assisted (HAE)
and Ultrasound-Assisted (UAE) methods. Two three-factor Rotatable Central Composite Designs were used to
assess the linear, quadratic, and interaction effects of the independent variables on the target responses. The
obtained results from both extraction systems revealed high ethanol percentages as the critical factor in
increasing tannin content. The optimum global processing conditions predicted by the polynomial models were
95.1 min, 46.4 ◦C, and 74.3% ethanol for HAE; and 18.7 min, 327.4 W, and 69.3% ethanol for UAE. Following
these conditions, 200 mg and 178 mg of total tannins per g of extract were recovered using HAE and UAE,
correspondingly. Although HAE presented a higher final response, the UAE stood out as a time-saving technique.