Alzheimer's disease (AD) is an irreversible brain disorder, which has been found to be associated with neurotoxic amyloid-β oligomers (AβO). The early diagnosis of AD is still a great challenge. Herein, inspired by the hierarchical channel structure of natural wood, we design and demonstrate a low-cost and sensitive wood channel-based fluidic membrane for electrochemical sensing of AβO1-42. In this design, Zn/Cu-2-methylimidazole (Zn/Cu-Hmim) with artificial peroxidase (POD)-like activity was asymmetrically fabricated at one side of the wood channels by biomimetic mineralization and a subsequent ion exchange reaction. The strong affinity between Cu(II) and AβO1-42 enables Cu(II) species in Zn/Cu-Hmim to be extracted by AβO1-42, thus suppressing the POD-like performance via Zn/Cu-Hmim disassembly. Using Zn/Cu-Hmim to catalyze the oxidation reaction of 2,2′-diazo-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) by H2O2, the current–voltage (I–V) properties of wood channels are influenced by the generated oxidation product (ABTS•+), thus providing information useful for the quantitative analysis of AβO1-42. Importantly, the three aggregation states of Aβ1-42 (AβM1-42, AβO1-42, and AβF1-42) can also be identified, owing to the affinity difference and available reaction sites. The proposed wood membrane provides a novel, assessable, and scalable channel device to develop sensitive electrochemical sensors; moreover, the sustainable wood materials represent alternative candidates for developing channel-structured sensing platforms.