The algebraic value of a chemical composition plays a crucial role in determining its physical properties, chemical reactivity, and biological activity. Algebraic graph theory investigates the connection between abstract algebra and graph theory. Focusing on the commuting graphs of semi-dihedral groups, we examine their various topological properties. Furthermore, we provide a detailed exploration of key topological graph indices, including the general Randi\'{c} index, the Wiener index, the atom-bond connectivity index (and its fourth variation), the Schultz molecular topological index, the geometric-arithmetic index, the harmonic index, and the Harary index. This research reveals the structural as well as mathematical features of these graphs, providing valuable insights into their possible applications.