GaAs has excellent optical, electrical, and mechanical properties and shows promise to be used in the fabrication of novel devices. However, the unprotected GaAs surface can release heavy metal compounds such as AsO x, which are toxic to living cells. A promising approach to reduce or eliminate this release relies on the passivation of the GaAs surface using different chemical approaches. In this work, we compared three different passivation methods aimed at enhancing the viability of cells on GaAs. Protective layers composed of self-assembled alkyl thiols, polypeptides, thick polymer layers, and shells of polyelectrolytes were tested. We confirmed that the GaAs surface can be made biocompatible for several days based on in vitro tests with HeLa and KB cells. In addition, we compared the cell spreading behavior on the GaAs substrates modified by different chemical approaches. Our results suggest that when the toxicity of the GaAs surface is reduced or eliminated, the cells' viability and spreading depend on the chemical and topographical nature of the surface.