Graph-based molecular structure descriptors (often called “topological indices”) are useful for modeling the physical and chemical properties of molecules, designing pharmacologically active compounds, detecting environmentally hazardous substances, etc. The graph invariant GRMα, known under the name general reduced second Zagreb index, is defined as GRMα(Γ)=∑uv∈E(Γ)(dΓ(u)+α)(dΓ(v)+α), where dΓ(v) is the degree of the vertex v of the graph Γ and α is any real number. In this paper, among all trees of order n, and all unicyclic graphs of order n with girth g, we characterize the extremal graphs with respect to GRMα(α≥−12). Using the extremal unicyclic graphs, we obtain a lower bound on GRMα(Γ) of graphs in terms of order n with k cut edges, and completely determine the corresponding extremal graphs. Moreover, we obtain several upper bounds on GRMα of different classes of graphs in terms of order n, size m, independence number γ, chromatic number k, etc. In particular, we present an upper bound on GRMα of connected triangle-free graph of order n>2, m>0 edges with α>−1.5, and characterize the extremal graphs. Finally, we prove that the Turán graph Tn(k) gives the maximum GRMα(α≥−1) among all graphs of order n with chromatic number k.