Abstract: Type 2 diabetes mellitus can be defined as a conformational disease since a beta cell producing protein called amylin undergoes a change in the tertiary structure followed by self-aggregation and deposition. Amylin deposition causes destruction of pancreatic β-cells. The aim of this study was to investigate whether different concentrations of magnesium and aluminium alter amylin conformation under near-physiological circumstances. Conformational variations were monitored by fluorescent method before and after incubation by shaker incubator in 37°C by LS55 spectrofluorometer instrument. This in vitro study showed that magnesium had contradictory effects on amylin folding and these effects were magnesium concentration dependent. Magnesium with concentration of 1 to 1.5 mM had inhibitory effect but in 2.5 to 3.5 mM promoted amylin misfolding significantly (p<0.05). The obtained data also demonstrated that aluminium with concentrations of 5, 10 and 20 μM had stimulatory effects on formation of beta-amyloid sheet significantly (p<0.05). It may be concluded that islet amyloid misfolding and cytotoxicity to β-cells might be magnesium dose dependent in diabetic patients.