Microglia cells are key players of the immune response in the central nervous system. Most brain probes encountered significant signal loss within six months due to protein absorption and microglia attachment. We used a vapor-based method to synthesize conformal coatings bearing anionic and/or cationic groups on complicate micro-structures. The interactions of polyionic polymer surfaces with microglia cells were investigated. After 24 h, the microglia cells were observed to reduce 22%, 35%, and 50% on the polyanionic, polycationic, and polyampholyte surfaces, respectively. Significant reduction of lamellipodia and filopodia formation was also observed on polycationic and polyampholyte surfaces, indicating the surface resistance of cell adhesion and cell spreading. After one week, the polyanionic, polycationic, and polyampholyte surfaces were observed to reduce cell adhesion by 20%, 45%, and 54%, respectively. The effectiveness of polyampholyte surface in resisting microglia adhesion was further analyzed through protein adhesion study and wettability tests. The polyampholyte surface provided consistent resistance against both laminin and BSA with protein absorption reduction of 70% - 85% after one week. The significant reduction of protein adhesion was attributed to the hydrophilic microenvironment created by the adjacent oppositely charged groups on the polyampholyte surface.