Objectives: The aims of this study were to compare the efficacy of two proven chemical disinfectants, glutaraldehyde and povidone iodine on dental impression and models by determining the reduction in the microbial load, and to compare changes in the physical properties of the models after adding the disinfectants. Materials and Methods: Irreversible hydrocolloid upper impressions of 90 patients were made and divided into 3 groups of 30 samples each; Group A––Control group; Impressions were run under clean tap water before pouring the model. Group B––2% Glutaraldehyde sprayed on the impression and left in situ for 10 min before pouring the model. Group C –10 ml of (5%) povidone iodine incorporated into the gypsum before pouring the model. Models from all three groups were subjected to microbiological assessment at three different time intervals, T0––24 h, T1––1 month and T2––3 months of storage by comparing the colony forming units (CFUs) of bacteria and fungi. The compressive strength of 5 models from each group was also analyzed in Newton's/mm2. Results: 2% Glutaraldehyde proved more effective than povidone iodine after 24 h of storage (T1), however at the end of 1 month (T1) and 3 months (T2) the Povidone group showed the maximum disinfection. Both the disinfectants caused a reduction in the compressive strength of the model with the povidone iodine group showing the maximum reduction. Conclusion: Although povidone iodine was the most effective disinfectant after 3 months, it showed a significant reduction in the compressive strength and caused discoloration of the model. 2% Glutaraldehyde proved to be the choice of disinfectant with minimal adverse effects.