Molecular structures are assigned numerical v-alues known as topological indices, which serve as important descriptors in chemical graph theory. In the present study, degree-based topological indices of the total graph of alkanes, a significant class of saturated hydrocarbons, are investigated. Several widely used indices, including the first and second Zagreb indices, Randić index, harmonic index, atom-bond connectivity index, forgotten index, sum connectivity index, symmetric division degree index, geometric–arithmetic index, and the first and second hyper Zagreb indices, are computed for the total graphs of linear alkanes. A detailed numerical comparison of these indices is presented along with their graphical behaviour as the carbon chain increases. Furthermore, regression analysis is performed to examine the relationship between the computed indices and selected physicochemical properties. The results highlight the influence of molecular structure on topological characteristics and demonstrate the applicability of total graph of alkanes-based descriptors in chemical graph theory, molecular modeling, and predictive chemistry.