Polyaniline (PANI) constitutes a very propitious conductive polymer utilized in several biomedical, as well as environmental applications, including tissue engineering, catalysis, and photocatalysis, due to its unique properties. In this study, nano-PANI/N-TiO2 and nano-PANI/Ag-TiO2 photocatalytic composites were fabricated via aniline’s oxidative polymerization, while the Ag-and N-chemically modified TiO2 nanopowders were synthesized through the sol–gel approach. All produced materials were fully characterized. Through micro-Raman and FT-IR analysis, the co-existence of PANI and chemically modified TiO2 particles was confirmed, while via XRD analysis the composites’ average crystallite size was determined as ≈20 nm. The semi-crystal structure of polyaniline exhibits higher photocatalytic efficiency compared to that of other less crystalline forms. The spherical-shaped developed materials are innovative, stable (zeta potential in the range from −26 to −37 mV), and cost-effective, characterized by enhanced photocatalytic efficiency under visible light (energy band gaps ≈ 2 eV), and synthesized with relatively simple methods, with the possibility of recycling and reusing them in potential future applications in industry, in wastewater treatment as well as in biomedicine. Thus, the PANI-encapsulated Ag and N chemically modified TiO2 nanocomposites exhibit high degradation efficiency towards Rhodamine B dye upon visible-light irradiation, presenting simultaneously high biocompatibility in different normal cell lines.