This study aimed to evaluate the effect of adding different concentrations of silver nanoparticles (AgNPs) on the flexural strength and microhardness of various denture base materials. For this study, a total of 60 specimens were used and divided into equal groups. The first group consisted of heat-cured acrylic resin (Vertex-Germany), while the second group consisted of thermoplastic resin (Breflex 2nd edition, Germany). The samples were created using a split brass mold with dimensions of 65 × 10 × 2.5 mm, in accordance with the specifications of the American Dental Association (specifically No. 12 for flexural and microhardness). Following this, the samples were divided into three groups (A, B, and C) based on different concentrations of AgNPs (0, 2, and 5%). The flexural and microhardness of the samples were assessed using a universal testing machine and the Vickers hardness test, respectively. The data were gathered, organized, and analyzed using statistical methods. The flexural strength findings showed a significant difference between the two groups. Also, there was a considerable decrease in the average value of the acrylic group as the concentrations of AgNPs rose, while the flexural strength of the thermoplastic group notably improved. Regarding microhardness, the results showed a significant difference between the two groups. It showed that the mean value of both groups increased with increasing concentrations of AgNPs. Within the limitations of laboratory testing conditions of this study, it was discovered that AgNPs negatively impact the flexural strength of acrylic resins. Furthermore, an increase in the concentration of AgNPs was found to be directly related to the flexural strength of thermoplastic resin and the microhardness of both groups. The concentration of AgNPs has a significant impact on certain mechanical properties of denture base materials, but it is important to consider their potential toxicity. How to cite this article: El-Hussein IG. Effect of Adding Different Concentrations of Silver Nanoparticles on Flexural Strength and Microhardness of Different Denture Base Materials. J Contemp Dent Pract 2024;25(5):417-423.