C-reactive protein (CRP) has become a recognized indicator of inflammation. CRP concentration in serum is an important indicator for monitoring early heart damage, and it is also a newly discovered coronary heart disease-associated inflammatory factor. A conductive nano-hybrid material composed of Au NPs and ionic liquid functionalized molybdenum disulfide (Au NPs/IL-MoS₂) was prepared and utilized to immobilize primary CRP antibodies. Subsequently, 1,5-diaminonaphthalene (DN) was adsorbed onto graphene oxide (GO) through π–π stacking, which was used to load iridium nanoparticles (Ir NPs) as a tag to label secondary CRP antibodies. The large surface area of Au NPs/IL-MoS₂ and the excellent electrocatalytic properties of Ir NPs/GO-DN toward the reduction of H₂O₂ resulted in a highly sensitive assay for CRP antigens. This immunosensor exhibited wide linear ranges from 0.01 to 100 ng mL⁻¹ and a lower detection of limit of 3.3 pg mL⁻¹ (S/N = 3). This CRP immunosensor can be applied in real serum sample analysis with satisfactory results, indicating that the immunosensor has potential applications in biomedical detection.