Polydiacetylenes (PDAs) have emerged as a promising class of stimuli-responsive materials due to their unique blue-to-red chromatic transition and associated fluorescence turn-on effect. These optical properties arise from the topochemical polymerization of diacetylene monomers into highly conjugated π-electron systems, enabling PDAs to function as dual-mode sensors. Their colorimetric and fluorimetric responses to external stimuli, including temperature, pH, mechanical stress, and chemical or biological interactions, have been widely exploited for sensing applications. PDA-based sensors have been developed for detecting volatile organic compounds (VOCs), metal ions, and pH changes, as well as for biological sensing of proteins, enzymes, and DNA. Additionally, PDAs have been utilized for environmental monitoring, including pollutant detection and mechanical strain assessment. A key strategy for enhancing PDA sensor performance involves adequate chemical modifications of the carboxyl-functionalized headgroup, which triggers a spectral change upon selective interactions with analytes. This review attempts to cover the strategies based on PDA headgroup modifications for tuning chromatic response, optical stability, and sensor efficiency, highlighting recent advancements and challenges. By exploring these modifications, this discussion aims to provide insights into the design of next-generation PDA-based sensors with improved performance and broader applicability.