Background Microleakage under orthodontic brackets has a role in early bracket debonding and white spot lesions due to the ingress of oral fluids in the bracket-adhesive-tooth interface. This in vitro study aimed to evaluate and compare the microleakage under orthodontic brackets bonded with the conventional adhesive system, nanocomposites, and nanoionomers. Materials and methods Forty-five human premolars were extracted for therapeutic reasons and collected for this study. Teeth were randomly assigned to three groups: Group A: conventional etching with conventional adhesive, Group B: conventional etching with nanocomposite, and Group C: conventional etching with nanoionomer. Stainless steel premolar brackets were used for bonding. After thermocycling, the extracted teeth were submerged in a 0.5% solution of basic fuchsine for 24 hours. They were then cut longitudinally. A stereomicroscope was used to assess microleakage along the occlusal and gingival interfaces. Results To compare the microleakage scores between gingival and occlusal aspects within each group, the student's t-test was performed. Analysis of variance (ANOVA) and the post-hoc Tukey test were applied to the data for intergroup comparison of microleakage scores. On comparing the microleakage scores, the gingival side of interfaces depicted higher microleakage than the occlusal side gingival side across all groups, demonstrating statistically significant results (P <0.05).On intergroup comparison, the occlusal bracket adhesive interface and gingival tooth adhesive interface revealed significantly higher microleakage values for Group B followed by Group C withGroup Athe least. However, there was no significant difference in the microleakage scores between Group B and Group C on intergroup comparison of mean microleakage scores(P <0.05). Conclusion The gingival side showed higher microleakage scores than the occlusal side. Nanoionomers showed microleakage values higher than the Transbond XT but lower than nanocomposites. Based on the results of thepresent study, in terms of microleakage, Transbond XT demonstrated lower microleakage when compared to nanoionomers and nanocomposites.