Human plasma fibrinogen (HPF) plays an essential role in the initial host response to biomaterials. Developing strategies for controlling the HPF biomaterial interactions is crucial but is still in its infancy. Here, it was demonstrated that the nanostructures on polymers such as needle like crystals (NLCs) and lamellar crystals (LCs) of isotactic polybutene 1 (iPB 1), as well as shish kebab crystals (SKCs) of high density polyethylene (HDPE), were capable of guiding the adsorption of HPF and their subsequent platelet adhesion. The NLCs of iPB 1, with a lateral dimension lower than the length of the HPF major axis, supported side on adsorption and trinodular conformation, confirmed by atomic force microscopy and quartz crystal microbalance with dissipation. Preferential alignment of HPF molecules concerning the axial direction of the NLCs was analyzed via an orientation analysis performed on single and multi protein levels. The results of the protein adsorption kinetic studies via quartz crystal microbalance revealed the surface dependent packing density and assembly configuration of HPF. To elucidate the relationship between single HPF adsorption and HPF layer formation, the dynamics of HPF assemblies adsorbed on nanostructured surfaces were investigated in situ by mapping using accumulated probe trajectories. Anisotropic diffusion of HPF was revealed on NLCs. This was ascribed to the partial detachment and thus the Sansetsukon like nanocrawling of HPF. To further understand the biofunctionality of the surface immobilized HPF, platelet adhesion as a function of surfaces and conformation was investigated. It was observed that the number of platelets adhered on NLCs was significantly reduced by 90% after one hour incubation, compared with those on LCs and SKCs. NLCs led to small platelet aggregates, which point toward the potential thrombogenicity of such nanostructured surfaces.