Background: Use of orthodontic bracket changes enamel surface properties and demineralization penetration (i.e. rougher surface, reduced hardness, and deeper demineralization). This study evaluated the correlation between the changed enamel surface roughness, micro-hardness and demineralization depth after orthodontic bracket use. Methods: Data were obtained from a previous research project involving 198 extracted human premolar teeth, which underwent standardized bonding and debonding procedures. Ninety-nine specimens were assessed for surface roughness before and after the bracket, measured as Ra (the arithmetic mean height in microns), and then underwent micro-hardness testing using the micro-Vickers hardness test. The remaining 99 specimens were exposed to a demineralization solution, and the demineralization depth was analyzed using scanning electron microscopy and ImageJ software. Pearson’s correlation coefficient was used to evaluate the relationship between enamel surface roughness, micro-hardness, and demineralization depth. Results: The findings revealed a weak positive correlation between enamel surface roughness and demineralization depth, which was not statistically significant (r = +0.151, p = 0.134). However, a significant moderate negative correlation was found between enamel surface micro-hardness and demineralization depth (r = −0.504, p < 0.01). Additionally, a significantly weak negative correlation was found between enamel surface roughness and micro-hardness (r = −0.289, p = 0.004). Conclusions: The impact of orthodontic bracket use on the enamel surface roughness and hardness mutually influence each other and contribute to deeper demineralization. Enamel surface roughness is inversely correlated with hardness, and its hardness is inversely correlated with demineralization depth. These findings have clinical implications as the effect on enamel surfaces and demineralization penetration complicates the reversal and management of lesions. The study highlights the need to explore less invasive alternatives to bonding and debonding procedures, conduct further research in this area and improve dental materials.