The formation of amyloids arises from the misfolding or unfolding of various proteins. This study investigated the impact of chemical chaperones, alpha-cyclodextrin (α-CD) and beta-cyclodextrin (β-CD), on the solubilization and defibrillation of sodium dodecyl sulfate (SDS)-induced myoglobin (Mb) amyloid fibrils. Amyloid fibril was developed in Mb in the presence of 0.8 mmol dm−3 SDS at pH 4.5. Subsequently, SDS-induced Mb amyloid was incubated with varying concentrations of α-CD and β-CD at the same pH. Our turbidity, intrinsic fluorescence, SDS-PAGE, and transmission electron microscope data showed that α-CD (2.1 mmol dm−3) was more efficiently solubilized the SDS-treated Mb aggregates than β-CD (4.0 mmol dm−3). But, another interesting phenomenon was observed with β-CD. The ThT fluorescence and far-UV CD data suggested that amyloid defibrillation by β-CD (0.6 mmol dm−3) was more effective than α-CD (0.9 mmol dm−3). The intrinsic fluorescence and far-UV CD data also showed that SDS-treated Mb regained native-like structure at lower α-CD compared to β-CD. Overall our data suggest that α-CD was more efficient in aggregate solubilization while β-CD was more effective in amyloid defibrillation. Understanding the mechanisms underlying cyclodextrins’ actions may serve as a basis for identifying potential drugs to suppress amyloid fibril formation effectively. This research provides valuable insights into mitigating amyloid-related pathologies.