Background: The aim of this study is to evaluate effects on stainless steel (SS) and zirconia implant drills of 50 cycles of sterilization through different processes. Methods: A total of 24 SS and 24 zirconia drills were treated with 3 different sterilization processes: 50 cycles of immersion in glutaraldehyde 2%, 50 cycles in 6% hydrogen peroxide and 50 cycles of heat. Energy-dispersive X-ray spectroscopy (EDX) was used to compare the effect of the different treatments compared to new untreated controls. Infrared thermography was used to measure the increase of temperature during drilling on bone ribs. A scanning electron microscopy (SEM) was used to measure the roughness of the samples. Results: Zirconia drills seem not to be affected by the different treatments; no significant differences were found with EDX nor through thermography controls. SS drills were affected by the different treatments, as confirmed by the increased roughness of the SS samples after all the cycles of sterilization/disinfection, measured at SEM. On the contrary, the zirconia drills roughness was not particularly affected by the chemical and thermal cycles. Significant differences were observed regarding the temperature, between steel and zirconia drills (p < 0.01). Conclusions: The disinfection agents had a weak impact on the temperature changes during implant bone preparation, while heat sterilization processes had no effect on either of the drills evaluated. The disinfection agents increased the roughness of the steel drills, while they had no effect on the zirconia drills.