Poly(3,4-ethylenedioxythiophene) (PEDT) is recognized as one of the most promising conducting polymers for future applications in the,fields of electronics, optics, energy storage/conversion and biomedical science. The toxicity of PEDT could be considered to affect the potential for its widespread application. Herein, the cytotoxicity and proinflammatory response of PEDT nanomaterials of three different shapes toward human lung fibroblast (IMR90) and mouse alveolar macrophage (J774A.1) cells are investigated. The shape-dependent toxicity of the PEDT nanomaterials is evaluated by examining cell morphological change, cytotoxicity, apoptosis/necrosis, oxidative stress, and immune response. The cytotoxicity and apoptosis of the nanomaterials increase with their decreasing aspect ratio in both cell lines. The formation of reactive oxygen species in cells treated with PEDT nanomaterials is dependent on the shape and concentration of the nanomaterial. Proinflammatory cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor a from macrophages, are induced by PEDT nanomaterial-treated cells.