3-Phenylthiophene-based water-soluble copolythiophenes (CPT9) were designed for colorimetric and fluorometric detection of lysophosphatidic acid (LPA) based on electrostatic interaction, hydrophobic interaction, and hydrogen bonding. Other negatively charged species gave nearly no interference, and the detection limit reached to 0.6 μM, which is below the requisite detection limits for LPA in human plasma samples. The appealing performance of CPT9 was demonstrated to originate from the multipoint interaction-induced conformational change of conjugated backbone and weakened electron transfer effect. To our best knowledge, this is the first polythiophene based optical sensor which displays emission peak red-shift followed with fluorescence enhancement.