Efficient cuttings transport is important for achieving safe and successful drilling operations. However, poor hole cleaning is considered to be one of the main issues that happens frequently in horizontal and highly deviated wells. The selection of the drilling fluids with enhanced rheological properties is one of the effective methods to increase cuttings transportation efficiency. The major purpose of the present research is to investigate the application of silica (SiO2) nanoparticles in improving hole cleaning in extended reach drilling (ERD) operations. Nanocomposite drilling fluids were prepared by adding silica nanoparticles into water-based mud (WBM) at different weight percent concentrations (0.1–1.5 wt%). The flow loop experiments were performed on a sophisticated purpose-built flow rig by circulating the tested fluid samples into the test section in a horizontal position, considering the influence of drill pipe rotation, flow rates, cuttings sizes, mud density, and drill pipe eccentricity. In addition, the study covers the impacts of laminar, transition, and turbulent flow regimes. The goal of such variation in the operational parameters is to simulate real field conditions. The results indicated that the addition of the silica nanoparticles to WBM increases the colloidal interactions with cuttings, therefore leading to a substantial enhancement in cuttings removal efficiency especially with the higher concentration of silica nanoparticles. It was shown that nanoparticles in drilling fluid increase cuttings transport by 20.32%–32.75% for different nanocomposite water-based drilling fluids used in this study. The proposed investigation demonstrates the feasibility of using silica nanoparticles in WBM to enhance the capability of drilling fluids in transporting and circulating drilled cuttings out of the wellbore. Furthermore, the results of this project would provide a more reliable understanding of the relationship between drilling operation parameters and hole cleaning performance in ERD operations.