Cholesterol and triglycerides are crucial essential materials in human anatomy for ensuring the stability and fluidity of cell membranes, as well as operating as a precursor for the formation of vital compounds such as hormones in the body, bile acids, and vitamin D. Although once the total cholesterol levels exceed some critical value, particularly in the form of the low-density lipoprotein, it can readily create massive blockage in the wall of the arteries resulting in the complications arising from coronary or ischemic heart disease and peripheral arterial disease. An ideal biocompatible electrochemical cholesterol biosensor should satisfy the criterions concerning with detection in the wide linear range of concentration, a low detection limit, superior sensitivity, a fast reaction time, and a decent reproducibility. The current review provides a brief legacy of a broad range of micro/nanostructured metal oxides (MOx) and their subsequent use for improving the analytical performance of electrochemical cholesterol biosensors over the last few decades. Pristine or hybrid metal oxides with micro/nanostructure morphology arising from ZnO, CuO2, CeO2, MnO2, TiO2, Co2O3, etc. show great promises as biosensors owing to their excellent electrical, electrochemical, and biocompatible characteristics. The enormous surface area of nanostructured-based MOx materials could offer an enhanced matrix for the immobilization of preferred enzyme, resulting in improved enzyme absorption per unit mass of constituents. In addition to highlighting recent achievements in this field, the inherent gaps associated with real-time applications of micro/nanostructured metal oxides (MOx) electrochemical biosensors, as well as their future prospects in clinical applications.