Introduction: Bonding of brackets with adhesives during orthodontic fixed appliance therapy is associated with white spot lesions (WSLs). An adhesive developed with an antimicrobial property is advantageous to prevent decalcification of the enamel surface. The current study assesses the antimicrobial and shear bond strength (SBS) characteristics of an experimental conventional orthodontic adhesive incorporated with different concentrations of nanoparticles (NPs) prepared from the leaves of Calotropis gigantea and compares them with non-admixed conventional adhesive.Materials and methods: A total of 40 premolar teeth therapeutically extracted for orthodontic purposes were randomly assigned to four equal groups of n = 10 each. In control Group I, unmodified conventional adhesive was used to bond the brackets. In the three experimental groups, Group II, Group III, and Group IV, the brackets were bonded with modified conventional adhesive admixed with the C. gigantea NPs in concentrations of 1%, 5%, and 10%, respectively. The agar well diffusion test and the disc agar diffusion (DAD) test were utilized for assessing the anti-microbial activity of the composite discs. The SBS of the groups was determined by a universal testing machine.Statistical analysis: A one-way ANOVA and Tukey's honestly significant difference (HSD) post-hoc test was used to analyze the difference in shear bond strength and microbial inhibition zone diameter between the groups with a probability (p) value of equal to or less than 0.05 as statistical significance.Results: The mean SBS for Group I without nanoparticles is 6.99±0.75 MPa. The SBS value decreased inversely in proportion to the concentration of NPs: Group II (1% NP) 6.29±0.67 MPa; Group III (5% NP) 4.40±0.47 MPa; and Group IV (10% NP) 1.98±0.21 MPa, which is statistically significant (p < 0.001). The incorporation of C. gigantea NPs resulted in a decrease in the actual microbial potency of the conventional adhesive.Conclusion: Isolated C. gigantea NPs, when used alone, proved to have antimicrobial efficacy, but orthodontic adhesives admixed with C. gigantea NPs showed no additive effect, and SBS values decreased with increased concentrations of NPs.