This chapter explores the profound effects of strong electric fields (EFs) on cytoskeletal proteins, specifically microtubules (MTs). MTs, crucial components of the cytoskeleton, exhibit unique electrical properties, including high electric charge and dipole moment of their subunit tubulin, making them highly sensitive to external EFs. Molecular dynamics simulations and experimental studies reveal that EFs can induce significant conformational changes, modulate rigidity, and affect the stability and polymerization dynamics of MTs. These alterations influence interactions with motor proteins such as kinesin and MT-associated proteins (MAPs), with frequency and intensity-dependent effects. Strong EFs have been shown to disrupt MT polymerization, promote disassembly, and impact MT-antibody interactions, suggesting potential therapeutic applications, particularly in cancer treatment by destabilizing the cytoskeletal framework. The effects of pulsed electric fields (PEFs) on MTs within cells are complex, varying with PEF parameters, cell type, and cellular environment. Studies demonstrate both direct and indirect mechanisms, with high-intensity PEFs causing microtubule depolymerization and structural destabilization. These insights highlight the potential of EFs in bio-nanotechnology, where controlling the spatial arrangement and function of cytoskeletal proteins is crucial. Further research is essential to elucidate the precise mechanisms underlying EFs interactions with cytoskeletal proteins, unlocking new therapeutic and biotechnological applications. This chapter underscores the significance of understanding the interplay between EFs and cytoskeletal dynamics, paving the way for innovative medical and technological advancements.