This paper describes a facile and reproducible protocol for the preparation of a supramolecular photodynamic therapeutic agent mediated by host–guest encapsulation in the absence of inorganic matrix. Two distinct approaches were explored to modulate the size and morphology of supramolecular nanoparticles (SNPs). One approach is through changing the guest integration components of biviologen derivatives during the self-assembly process. It provides the opportunity to modulate the morphology (from amorphous to spherical) and the size of the self-assemblies (from 100 to 600 nm) by simply adjusting the length of the guest components. The other approach is a facile oil-in-water emulsion-phase method to synthesize high-quality supramolecular photodynamic therapeutic agents with good dispersion and uniform morphology in aqueous solution. In particular, photosensitizing efficiency was compared and the results revealed that this kind of particles exhibited higher photo-oxidation efficiency than the pure porphyrin derivative at the same concentration. Furthermore, the confocal microscopic images revealed the SNPs can be successfully endocytosed by Hela cell at various concentrations. In addition, the MTT assay indicated cell viability was not hindered by the concentration of SNPs up to 3.2 mg mL⁻¹ before light irradiation, thereby revealing good biocompatibility and remarkably low cytotoxicity of SNPs in vitro. Importantly, the cell viability was significantly attenuated to ∼20% after light irradiation (633 nm) for 1 hour. These SNPs would thus be promising materials as supramolecular photodynamic therapeutic agents in the treatment of cancer.