Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) requires a matrix, and traditionally small organic matrices (SOMs) carrying acidic or basic functional groups are used. However, the analyte ionization via secondary processes in the gas-phase seems to be more important than primary processes. For conjugated polymeric matrices, an even more complicated picture emerges due to their apolar and aprotic nature, high molecular weight, and low tendency to desorb. Poly(3-dodecylthiophene-2,5-diyl) (P3DDT), a good matrix for low-molecular weight (LMW) analytes, does not give matrix-related peaks in the LMW area. Here, carboxylic acid (-COOH) side-chains are introduced via postpolymerization modification. The polymers are characterized by NMR, FT-IR, CV, MALDI MS, and, when possible, GPC. The electron withdrawing side-chains serve three functions; i) raising the ionization potential (IP), ii) improving the absorption maximum, and iii) acting as a source of protons. When measuring basic amines, this results in the occurrence of additional [Analyte + H⁺]⁺ signals compared to polymers without acidic groups, where only radical cations [Analyte]^+• are detected. Similarly, estradiol and testosterone, compounds with high IPs, are not detected by polythiophenes without acidic groups, while P3DDT-COOH enables detection as protonated species.