A sustainable hybrid material based on carbonized cotton cloth/zeolite imidazolate framework-71/Fe₃O₄/polythionine (CC/ZIF-71/Fe₃O₄/PTh) was synthesized and applied in ultrasound-assisted dispersive magnetic solid-phase extraction (USA-DMSPE) followed with high performance liquid chromatography-ultraviolet detection (HPLC-UV) for simultaneous quantitation of diclofenac (DIC) and febuxostat (FEB) in human plasma. The surface of CC was modified with nanoarrays of zeolite imidazolate framework-71/Fe₃O₄/Polythionine. At first, an in situ synthesis of ZIF-71 in the presence of CC was carried out, and followed with magnetization process and oxidative polymerization of thionine. The nano-modifier agents improved the merits of the sorbent involving stability, porosity, mast transfer, π–π interactions and selectivity of CC. Characterizations of the hybrid sorbent were examined with different instrumental techniques. The limits of detection (LODs, S/N = 3) were recognized 2.1 ng mL⁻¹ for DIC and 3.7 ng mL⁻¹ for FEB. Acceptable linearity (0.992 ≤ r² ≤0.996) and relatively broad dynamic ranges of 10.0–1800.0 ng mL⁻¹ and 15.0–2500.0 ng mL⁻¹ were achieved for DIC and FEB, respectively. Reasonable intra-assay (≤7.2%, n = 9) and inter-assay (≤7.5%, n = 9) precisions as well as appropriate accuracies (≤8.0%) were provided illustrating applicability of the current approach for analytical purposes. Eventually, CC/ZIF-71/Fe₃O₄/PTh was employed as four-part sorbent for the assessment of DIC and FEB in human plasma at trace levels and subsequently main pharmacokinetic data such as T_1/2, T_max, C_max, and AUC_0–24 of these drugs were comprehensively investigated.