Aim: The aim of the present study to test the effectiveness of microwave irradiation on the disinfection of gypsum casts and to evaluate its effect on the diametral tensile strength (DTS) of type III and type IV dental stones. Methodology: In the present study, a total number of forty specimens were used; where 20 were composed of type III dental stone and 20 were composed of type IV dental stone. Each main group was then subdivided into 4 subgroups according to the type of treatment received, group I and II received microbial treatment; whereas groups III and IV received Mechanical treatment. Results: Results revealed that the median count of S. aureus (n=5) was 2 x 104 cfu/ml and that of P. aeruginosa (n=5) was 1.5 x104 cfu/ml for the type III dental stone cast samples. After microwave irradiation, the median count was 0 cfu/ml in both cases (p-value of 0.042 and 0.041 respectively). As for the type IV dental stone cast samples the median count of S. aureus (n=5) was 1.5 x 104 cfu/ml and that of P. aeruginosa (n=5) was 1 x104 cfu/ml. After microwave irradiation, the median count was 0 cfu/ml in both cases (p-value of 0.038 and 0.039 respectively). Regarding DTS tests, results revealed that the mean DTS for the control (n=5) and microwave irradiated (n=5) samples of the type III dental stone were 20.99 (± 1.76) and 27.37 (± 1.67) MPa respectively (p-value 0.00),while DTS values for the control (n=5) and microwave irradiated (n=5) samples of the type IV dental stone were 27.74 (± 2.81) and 36.48 (± 1.78) MPa respectively (p-value 0.00). Conclusion: Microwave irradiation for 5 minutes (at 900W and 2450 MHz) is sufficient for the disinfection of dental casts, constructed from type III and type IV dental stone. In the samples that were not subjected to microwave irradiation, type IV dental stone has a higher DTS values than type III dental stone. Microwave irradiation resulting in an increase in the DTS of both type III and type IV dental stones.