Herein, we report a unique design of a flexible PVDF film with copper tannic acid (Cu-TA) coordination nanosheets for piezo-catalysis and biomolecule detection. The composite film was obtained by mixing Cu-TA nanosheets with PVDF solution and casting into membrane films. Its piezo-catalytic nature was evaluated by oxidizing colorless TMB into blue colored oxTMB under ultrasonic irradiation. This process promotes more release of •OH from decomposition of H₂O₂ which behaves like peroxidase activity. The chromogenic nature can be employed for colorimetric detection of selective biomolecules such as Ascorbic acid (AA), glutathione (GSH) and Cystine (Cys). Our results show that the Cu-TA/PVDF composite film exhibit a favorable performance in biomolecule detection with a limit of detection (LOD) to AA (5.7 μM), GHS (0.46 μM), and Cys (0.89 μM). We analyzed GSH and Cys. nd Cys in tap water samples and commercial vitamin-C tablets for AA. The proposed piezo-catalytic composite can be used to design highly sensitive sensors for detecting different biomolecules in biomedical applications.