Topological index and molecular structure are cardinal topics in graph theory that connect many real-life situations. Mathematical chemistry is a part of theoretical and computational chemistry in which the assertion is primarily based on the mathematical tool rather than focusing on quantum mechanics. The main concept behind the topological indices is that they relate to various non-identical physicochemical characteristics of chemical compounds. Topological indices are utilized to examine the molecular structure of a chemical compound. These topological indices correlate the molecular properties of graphs, such as boiling point, melting point, temperature, pressure, heat of evaporation, chemical reactivity, biological activity and so on. The integration of graph theory and chemistry plays a dominant role in many fields. Topological indices are extensively used in computational chemistry and the pharmaceutical industry for manufacturing new medications, particularly in the areas of toxicology, risk assessment and drug design. In this research paper, the computation of the Sombor index, harmonic index, inverse sum index and symmetric division deg index of a simple connected graph called the thorn graph is analyzed relating to the thorn family, namely thorn ring, thorn path and thorn star and thorn multi-star. The primary objective of this research work is to connect the thorn graph with the topological indices to facilitate numerous real-time applications. © (2023), (International Association of Engineers). All Rights Reserved.