This study numerically examined the impacts of central winglets and Al2O3-water nanofluid on the thermo-hydraulic performance in a zigzag channel. The analyzes based on Computational Fluid Dynamic (CFD) using the SIMPLE algorithm are actualized for nanofluid flow in Reynolds numbers (Re) varying between 200 and 1200. The volume fraction of nanoparticle (φ) is changed from 1% to 5 %. The upper and lower zigzag surfaces are kept at Tw = 350 K constant temperature. The results are given in terms of thermal improvement (η), dimensionless friction factor (Γ), and thermo-hydraulic performance (THP). In addition, the work is compared with the zigzag channel without winglet for the base fluid. The temperature and velocity distributions are obtained for the zigzag channel with and without winglet at different Reynolds numbers. The results show that the nanofluid and winglets contribute considerably to the enhancement of heat transfer, but the friction factor slightly increases. The heat transfer improves with increasing inlet velocity and particle volume fraction. The highest thermo-hydraulic performance is obtained as approximately 2.12 for Re = 400 and φ = 0.05.