The exploration of new reactivity modes and synthetic methods has always been an attractive goal of organic and medicinal chemistry. As potential raw materials for the efficient construction of nitrogen- and sulfur-containing heterocycles, isatins and thioisatins have a wide range of applications in biomedicine and polymer materials. However, traditional synthetic methods are mainly limited to the reaction at the C3-position of isatins and thioisatins. This review summarises the recent advances in cyclization reactions induced by the C–N or C–S bond cleavage of isatins or thioisatins in the last 5 years, which display a distinct reactivity mode from traditional methods. In addition, this review introduces five approaches to C–N or C–S bond cleavage and emphasises their potential applications to the production of important intermediates in total synthesis, medicine, and materials.