One of the most effective oral antipyretics and analgesics, ibuprofen (IBP) is a primary ingredient in hospital wastewater because it is widely used to treat both acute and chronic pain. It is important to detect its concentration in the wastewater. Bio-electrochemical sensor is a promising detection method due to its durability and accuracy. Schiffbase is an advanced electrode materials for bio-electrochemical sensor. Which able to detect (IBP) concentration in wastewater.2,3dihydroxy-N'1-((E)-2-hydroxybenzylidene)-N'4-((Z)-2-hydroxybenzylidene (Schiffbase) materials have been synthesized and characterized.IR spectroscopy data identified (OH/H2O), ʋ (H-bonding), ʋ (C = O), ʋ (COH), ʋ (C = N) function groups. The SEM images of Schiff base presented needle-like shape with regular morphology. Electrochemical electrode have been fabricated from Schiffbase materials. IBP detected electrochemically by CV, DPV, and EIS methods, sensing rate of (2E−7 A/mgL−1) with coefficient of determination was (R2 = 0.999), into two steps sensing mechanism, which correspond to the ion diffusion process, respectively. Schiffbase electrodes shows superior sensitivity for low concentration of IBP (~ 2 mg/L). Sensing mechanism proposed upon electrochemical results.