Covalent organic frameworks (COFs) are crystalline nano/microporous materials assembled from organic molecules through covalent bonds. Having various advantages such as large surface area, fully conjugated structure, and being in atom-thick dimensions makes COFs a promising candidate for numerous applications such as energy storage, electrocatalysis, and electrochemical devices. Yet, their potential for facilitating biosensor design and bioelectrochemical processes has not extensively been investigated. Therefore, in this study, we harnessed the simplicity, enhanced conductive property, and organic nature of COFs in electrochemical enzymatic biosensor design that aimed to detect superoxide radicals as a model system. Two different triazine-based COFs, CTF-1 and TRITER-1, were successfully synthesized and characterized using Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and transmission electron microscopy (TEM). Electrochemical studies demonstrated that CTF-1 improves the electrochemical performance of the enzymatic biosensors and is suitable for electrode design. Using the developed CTF-1-based biosensor that uses superoxide dismutase (SOD) as recognizing element, we measured the levels of superoxide anions, which are known to include in carcinogenesis process, with 0.5 nM detection limit.