Here, five novel polyamides (PAs) containing ether linkages, xanthene, and fluorene rings have been successfully prepared via the one-step solution polymerization of a cardo-type diamine monomer based on xanthene and different commercial dicarboxylic acids. All polymers presented good solubility in aprotic polar solvents and had inherent viscosity within the range of 0.64–0.89 dL g−1. The PAs indicated good heat resistance with 10% weight loss temperatures (Td10%) in the range of 417–536 °C, more than 58% residue at 700 °C, and high glass transition temperatures (Tg) of 208–281 °C in N2 gas. A remarkable antiproliferative effect was exhibited toward A431 cells using pyridine-2,6-dicarboxylic acid-derived PA (IC50 = 18.7 μM, viability inhibition = 94.49%). In addition, the facile synthetic route was used for the fabrication of a polymer nanocomposite (PA-4/ZnO@PMT) with enhanced thermal and optical properties via grafting functionalized ZnO nanoparticles (ZnO NPs) onto one of the PAs (PA-4). To disperse the ZnO NPs well and increase interactions between the two phases, the surface of the NPs was modified with a silane coupling agent. The inhibition potencies of PA-4 and PA-4/ZnO@PMT were checked against six bacterial species. It was found that the nanocomposite showed better activities against the microorganisms. PA-4/ ZnO@PMT with a cross-linked network structure and PAs as absorbents were introduced for methylene blue (MB) dye removal from aqueous solution. The prepared nanocomposite indicated higher capabilities for the extraction of MB dye compared to the polymer without a filler