Sweat is considered the most promising candidate to replace conventional blood samples for noninvasive sensing. There are many tools and optical and electrochemical methods that can be used for detecting sweat biomarkers. Electrochemical methods are known for their simplicity and cost-effectiveness. However, they need to be optimized in terms of selectivity and catalytic activity. Therefore, electrode modifiers such as nanostructures and metal–organic frameworks (MOFs) or combinations of them were examined for boosting the performance of the electrochemical sensors. The MOF structures can be prepared by hydrothermal/solvothermal, sonochemical, microwave synthesis, mechanochemical, and electrochemical methods. Additionally, MOF nanostructures can be prepared by controlling the synthesis conditions or mixing bulk MOFs with nanoparticles (NPs). In this review, we spotlight the previously examined MOF-based nanostructures as well as promising ones for the electrochemical determination of sweat biomarkers. The presence of NPs strongly improves the electrical conductivity of MOF structures, which are known for their poor conductivity. Specifically, Cu-MOF and Co-MOF nanostructures were used for detecting sweat biomarkers with the lowest detection limits. Different electrochemical methods, such as amperometric, voltammetric, and photoelectrochemical, were used for monitoring the signal of sweat biomarkers. Overall, these materials are brilliant electrode modifiers for the determination of sweat biomarkers.