Polydimethylsiloxane （PDMS） optical waveguides have a wide range of biomedical applications due to their excellent biocompatibility. In order to improve the refractive index of PDMS to improve the application limitations of PDMS optical waveguides, PDMS-TiO₂ organic-inorganic nanocomposites were prepared by in situ sol-gel method using terminal hydroxyl polydimethylsiloxane （PDMS-OH） and titanium tetramethoxymethane isopropoxide（TTIP） as the main raw materials. By changing the mass ratio of PDMS-OH to TTIP, uniform and transparent PDMS-TiO₂ solutions with different refractive indices were obtained, and the refractive indices of the materials were characterized by ellipsometry after the curing of the solutions into films, and the refractive indices were increased from 1.40 to 1.591 at 589 nm. Using the soft embossing technique, the core and cladding layers of waveguides were made of PDMS-TiO₂ and PDMS, respectively. A flat plate-type multimode waveguide with a cross-section of 5 cm × 80 μm was prepared, and the average transmission loss was measured to be 0.713 dB/cm when the input wavelength was 633 nm.This study provides a new reference for the application of PDMS optical waveguides in biomedical fields.