The wide usage and subsequent leakage of nonsteroidal anti-inflammatory drugs (NSAIDs) into the environment present an urgent need to create materials for selective binding of NSAID drugs, which are highly similar to one another in structure and functionality. Surface–core double-cross-linking of cationic micelles containing Naproxen or Indomethacin as the template yielded molecularly imprinted nanoparticles (MINPs) for these drugs. The nanoparticle receptors resembled water-soluble proteins in their hydrophilic exterior and hydrophobic core with guest-tailored binding pockets. Their binding selectivity for their templates over other NSAID analogues rivaled that of antibodies prepared through much lengthier procedures.