During impressions, bacteria, viruses, and fungi remain on the impression material, representing a significant risk for the medical team (dentists, dental assistants, and laboratory technicians). Impression disinfectants have been introduced into dentistry to reduce the risk of cross-infection. This study was performed by examining the surface disinfection of five commonly used impression materials in prosthodontics: alginate-Tropicalgin (Zhermack^®), condensation silicone-Zetaplus (Zhermack^®), Oranwash L (Zhermack^®); and addition silicone-Elite HD + Putty Soft (Zhermack^®), Elite + Light Body (Zhermack^®) after the disinfection with three disinfectants: Zeta 3 Soft (Zhermack^®), Zeta 7 Spray (Zhermack^®) and Zeta 7 Solution (Zhermack^®). Before disinfection, the impression materials were contaminated with Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, and Candida albicans ATCC 10213. Our results demonstrate the efficacy of the two examined specific disinfectants in reducing cross-infection risk. The surface disinfectant-spray is not adequate for impression disinfection. A high number of bacterial colonies were found on the surface of all impressions disinfected with this spray. The immersion-disinfection method effectively eliminates the risk of cross-infections (Kruskal–Wallis test showed a p < 0.001).