A novel cystamine-based hybrid, namely, α-[NH3(CH2)2SS(CH2)2NH3PbI6]·2H3O (1a), was prepared under solvothermal conditions. Interestingly, 1a, which is built up from isolated PbI6 octahedra, can be easily changed into its polymorph, namely, β-[NH3(CH2)2S–S(CH2)2NH3PbI6]·2H3O (1b) only by heating it up to 45 °C. According to the results of X-ray diffraction analyses, the polymorphic phenomenon of 1a and 1b results from a conformational change in the helical diprotonated cystamine cation in the solid state. Both 1a and 1b crystallized in the orthorhombic Pna21 space group. The reversibility of this transformation is proved by single-crystal X-ray diffraction and second harmonic generation measurements.