We report the highly sensitive and selective acetone detection achieved by sensitizing p-type Co3O4 nanofibers (NFs) with Ir nanoparticles (NPs) and graphene oxide (GO) sheets for potential diagnosis of diabetes. Co3O4 NFs mixed with Ir NPs (1 wt%, average particle size 6 nm) were further functionalized by GO sheets (1 wt%) to investigate the dual-sensitization effect on cross sensitivity for acetone, pentane, NO, NH3, CO, and NO2. These Ir- and GO-co-functionalized Co3O4 NF composites exhibited a high acetone response (Rgas/Rair = 2.29) at 5 ppm. This value was 58% and 36% greater than that of the pristine Co3O4 NFs (Rgas/Rair = 1.45) and Ir-functionalized Co3O4 NFs (Rgas/Rair = 1.69), respectively. The detection limit of Ir- and GO-co-functionalized Co3O4 NF sensors is predicted to be as low as 120 ppb, presenting the response value of 1.18 at 300 °C. Furthermore, superior acetone selectivity, in competition with interfering gases such as pentane, NO, NH3, CO, and NO2, was investigated. This work demonstrates that optimized co-sensitization of two catalysts (i.e., Ir NPs and GO sheets) on p-type metal oxide NFs enables the precise detection of exhaled breath gases for the diagnosis of diabetes.