In minimally invasive surgery, the tendency for human tissue to adhere to the electrosurgical scalpel can complicate procedures and elevate the risk of medical accidents. Consequently, the development of an electrosurgical scalpel with an anti-sticking coating is critically important. Drawing inspiration from nature, we identified that the leaves of Setaria Virids exhibit exceptional non-stick properties. Utilizing this natural surface texture as a model, we designed and fabricated a specialized anti-sticking surface for electrosurgical scalpels. Employing nanosecond laser direct writing ablation technology, we created a micro-nano textured surface on the high-frequency electrosurgical scalpel that mimics the structure found on Setaria Virids leaves. Subsequently, a TiO2 coating was deposited onto the ablated scalpel surface via magnetron sputtering, followed by plasma-induced hydrophobic modification and treatment with octadecyltrichlorosilane (OTS) to enhance the surface’s affinity for silicone oil, thereby constructing a self-lubricating and anti-sticking surface. The spreading behavior of deionized water, absolute ethanol, and dimethyl silicone oil on this textured surface is investigated to confirm the effectiveness of the self-lubrication mechanism. Furthermore, the sticking force and quality are compared between the anti-sticking electrosurgical scalpel and a standard high-frequency electrosurgical scalpel to demonstrate the efficacy of the nanosecond laser-ablated micro-nano texture in preventing sticking. The findings indicate that the self-lubricating anti-sticking surface fabricated using this texture exhibits superior anti-sticking properties.