Purpose: The purpose of this study was to evaluate the effect of different denture cleaning regimens on surface roughness of denture base material and bond strength to hard reline material.Materials and methods: 100 disk-shaped specimens were prepared from a denture base resin and immersed into the following five groups (n=20): Group C: Corega Tabs, Group P: Protefix Tabs, Group CU: ultrasonic device with Corega Tabs and Group PU: ultrasonic device with Corega Tabs, and Control: distilled water. All cleaning protocols were applied for 90 times to each specimen according to the instructions of the manufacturers. Surface roughness values were measured using a profilometer and surface evaluations were performed with scanning electron microscope (SEM). Reline materials were applied on the specimens and shear tests were performed using a Universal Testing Machine. Data were analyzed using One-way ANOVA and Tukey's post hoc tests were used for comparison among groups with a significance level of 0.05.Results: Group PU and group CU showed significant increase in surface roughness values compared to group P, C, and Control (p<0.05). Control group showed significantly lower shear bond strength values compared to the other groups (p<0.01). Group P exhibited higher shear bond strength values compared to group C (p=0.003). No significant differences were found between group P and PU (p=0.945), same results were found between group C and CU (p=0.283).Conclusion: Using denture cleansers with ultrasonic devices significantly affected the surface topography of denture bases. All tested cleaning regimens increased the bond strength of hard reline material to the denture base.