Amyloidosis causes organ dysfunction due to deposition of β-sheet structured amyloid fibrils in multiple organs. Drugs that break up amyloid fibrils (amyloid breakers) is considered as promising therapy for amyloidosis, but none is yet clinically available. Recently, we performed in vitro fluorescence-based high throughput screening (HTS) (1280 compounds) to identify small molecules that interact with a mutant transthyretin (TTR), a causative protein of hereditary ATTR (ATTRm) amyloidosis. Here, we focused on the HTS-derived nineteen hit compounds and identified two compounds (B and R) that decrease preformed mutant TTR amyloid fibrils. We next validated 113 analogs harboring common basic chemical structure with compound B, and demonstrated that 12 compounds significantly disrupt preformed mutant TTR amyloid fibrils. Importantly, among these 12 compounds, several compounds also broke preformed amyloid fibrils derived from amyloid-β (Aβ) and tau proteins, well-known amyloid causative proteins in Alzheimer's disease. Finally, some of the hit compounds are the component of natural products with low cytotoxicity. Overall, the study will be of great interest for the development of not only therapeutic drugs but also healthy supplements that are applicable for amyloidosis.