The suggested work brings a novel knowledge of an electric-induced mass transfer occurring during the gel electro-membrane extraction (G-EME) followed by HPLC UV detection. The natural deep eutectic solvent(s) (DESs), such as choline chloride mixed with itaconic acid (mole ratio 1:1) and choline chloride mixed with methacrylic acid (mole ratio 1:1), were used as the green additives in the agarose gel membrane. The impact of DESs was tested for the extraction of codeine, dasatinib, imatinib, morphine, and nilotinib from human plasma and urine samples. The DESs were incorporated into silica nanoparticles (SiNPs) through porous polymerization to form a SiNPs@P(DES), subsequently dispersed in the gel structure. As a result, the agarose membrane was stabilized, extraction efficiency increased, and the EEO flow diminished. In addition, testing of nonporous polymerization versus porous polymerization showed that extraction efficiencies are higher using the latter approach due to the higher surface area of the porous SiNPs@P(DES). The optimal extraction conditions were found to be 3.0 % w/v agarose gel (pH 3.5) containing 0.02 % w/v SiNPs@P(DES), applied voltage at 60 V, extraction time at 10 min, pH of the donor phase at 6.0, and pH of the acceptor phase at 4.0. The obtained extraction recoveries were in the range of 88.1–92.9 %. The limits of detection (LODs) and quantification (LOQs) were 1.6–14.5 ng mL⁻¹ and 5.3–47.8 ng mL⁻¹, respectively. The intra- and inter-day repeatability (n = 4) were within 3.3 % and 6.4 % RSD, respectively.