This paper presents the first part of a study that aims at developing an optimized microwave-assisted method for extracting the lignan secoisolariciresinol diglucoside from defatted flaxseed meal. Two-level fractional factorial designs were used for screening the following factors: the microwave power level (30–360 W), the time of residence in the microwave cavity (1–25 min), the concentration of NaOH (0.25–1 M), and the mode of microwave power application (power on 30 and 60 s/min). The experimental domain had to be adjusted after each screening in order to focus the future optimization study within the factors' ranges likely to contain the optimal extraction conditions.