Aim and objective: The prevalence of dentinal hypersensitivity after tooth preparation is high and there is a need to explore the usage of contemporary agents in prosthodontics for this purpose. Therefore, the present study aims to evaluate the retention of fabricated copings on prepared teeth coated with freshly prepared arginine-calcium carbonate-fluoride and casein phosphopeptide (CPP)-amorphous calcium phosphate-fluoride desensitizing agents. Materials and methods: Forty-five extracted premolar teeth were mounted in autopolymerizing acrylic resin and prepared for complete cast metal copings following the standardized protocol. These preparations were randomly divided into three groups for the application of desensitizing agent: arginine based, CPP based, and control (without any agent). Each group was further subdivided into three and luted using either glass ionomer (GIC), resin modified glass ionomer (RMGIC), or resin cement. All these specimens were subjected to tensile bond strength evaluation using a universal testing machine. Results: The mean bond strengths (in Newtons) in the control group were 308.62 ± 58.84, 176.89 ± 35.46, and 300.35 ± 27.9 with GIC, RMGIC, and resin types of cement, respectively. On the application of arginine-based desensitizer, the bond strengths decreased to 90.26 ± 10.68, 85.07 ± 18.82, and 236.05 ± 43.62 with GIC, RMGIC, and resin types of cement, respectively. On the other hand, on the application of CPP-based desensitizer, the bond strengths in the same order of luting were 272.32 ± 30.5, 203.47 ± 60.57, and 158.66 ± 25.32. Conclusion: Arginine-based desensitizer did not influence the retention of crowns with resin cement, whereas CPP-based coat did not affect the retention of crowns luted with GlC as well as RMGIC. Clinical significance: The present study shows the importance of choosing a desensitizing agent based on the luting cement selected for prosthesis retention.