Guanine and poly(methyl methacrylate) (PMMA) layers 60 nm thick were fabricated by physical vapor deposition and spin-coating, respectively, for potential application as bio-based field-effect transistors. A few layers of graphene on a variety of non-flexible and flexible supports were used as substrates for the guanine and PMMA layers. The interactions between these layers and graphene were studied and their effects on the electrical properties of the graphene were monitored over an extended period of time. Guanine had no noticeable effects on the transport properties of graphene. The presence of PMMA reduced the charge-carrier mobility of graphene by up to 42%. This combination has potential for use as a device in biosensors, environmental science, computer-processing, and graphene-based electronics.