Functionalized crystalline solids based on metal–organic frameworks (MOFs) enable efficient luminescence detection and high proton conductivity, making them crucial in the realms of environmental monitoring and clean energy. Here, two structurally and functionally distinct zinc-based MOFs, [Zn(TTDPa)(bodca)]·H2O (1) and [Zn(TTDPb)(bodca)]·H2O (2), were successfully designed and synthesized using 3,6-di(pyridin-4-yl)thieno[3,2-b]thiophene (TTDPa) and 2,5-di(pyridin-4-yl)thieno[3,2-b]thiophene (TTDPb) as ligands, in the presence of bicyclo[2.2.2]octane-1,4-dicarboxylic acid (H2bodca). Both 1and 2display a three-dimensional (3D) structure with 5-fold interpenetration, and notably, 2forms a larger one-dimensional pore measuring 17.16 × 10.81 Å2in size. Fluorescence experiments demonstrate that 1and 2can function as luminescent sensors for nitrofurantoin (NFT) and nitrofurazone (NFZ) with low detection limits, remarkable selectivity, and good recyclability. A comprehensive analysis was conducted to investigate the differing sensing effects of compounds 1and 2and to explore potential sensing mechanisms. Additionally, at 328 K and 98% relative humidity, 1and 2exhibit proton conductivity values of 2.13 × 10–3and 4.91 × 10–3S cm–1, respectively, making them suitable proton-conducting materials. Hence, the integration of luminescent sensing and proton conductivity in monophasic 3D Zn-MOFs holds significant potential for application in intelligent multitasking devices.