Exploring facile analytical technologies with high reliability and precision to quantify targets is significant but remains great challenge for disease diagnosis. Several signal transduction pathways have stimulated the development of various target analysis system. However, many systems are limited by the single channel/mechanism method, it could lead to false positive/negative results. Herein, a dual channel-driven fluorescence sensor was designed for simultaneously analysing homovanillic acid (HVA) and Al3+, two effective indicators for the diagnosis of Parkinson's disease (PD). With two steps of postsynthetic modification (PSM) strategy for covalent organic framework (COF) TpBD-(OH)2, the excellent luminescent material TpBD-(COOH)2@EuTTA (1) still maintained good structural stability, further prepared hydrogel had also been applied to dual channel detect two analytes related to PD. The fluorescence sensor showed turn-off fluorescence response to HVA, and exhibited ratiometric identification approach to Al3+. Simultaneous and quantitative detection with dual channel for two indicators can greatly improve the accuracy of the diagnosis of PD. This study not only provides feasible strategy for versatile functionalization of COFs, but also reveals promising perspectives for the future of non-invasive and accurate disease diagnosis.