Objectives: Coating orthodontic brackets with metal nanoparticles seem to affect surface roughness and friction. We aim to compare the effects of coating brackets with copper oxide (CuO), titanium dioxide (TiO2), and silver hydroxyapatite (S-HAP) on friction between brackets and various sizes and materials of orthodontic wires. Material and Methods: In this experimental study, we selected four groups of stainless steel (SS) brackets with eight orthodontic wires (SS and nickel-titanium [Niti]) in different sizes. Three groups were coated with CuO, TiO2, and S-HAP nanoparticles using dip coating. Then, we attached a 100 g weight to the wires and hung it from the universal testing machine. The wire passed through the brackets at a speed of 0.5 mm/min for 25 s. Finally, the friction between wires and brackets was compared using a two-way analysis of variance. Results: The results showed that friction of brackets coated with TiO2 was significantly lower than S-HAP (P = 0.021) and did not differ significantly between CuO and the control (P = 1). Furthermore, friction between CuO brackets was not significantly different from other groups (P > 0.05). Niti round wires had significantly lower friction with all brackets compared to 0.16 × 0.22 square inch Niti wire (p< 0.05), which, in turn, showed significantly lower friction compared to 0.16 × 0.22 square inch stainless steel (SS) wire (P = 0.008). Conclusion: Coating brackets with TiO2 and CuO nanoparticles can reduce the friction Moreover, Niti round wires show the least friction compared to rectangular or SS wires with all types of brackets.