Abstract Reduced‐graphene‐oxide layers (rGO) offer extremely subtle transducer thin‐films and can be unified in interdigital micro‐electrodes for various purposes. Understanding the functions and nature of rGO specially bio‐compatibility, we can use this as potent‐tool for the detection of antibiotic‐drug Rifampicin (RFP) in standard/pharmaceutical samples. Herein, we synthesize CuO@rGO nano‐composite and explored its potency for the preparation of electrochemically‐active‐electrodes. Catalytic‐activity of as‐synthesized CuO@rGO nano‐composite is checked in 1.0 mM of Fe 2+/3+ solutions and found to be more than three times higher current as compared to bare, rGO or CuO modified GCE. Subsequently, modified electrodes are used to detect RFP via two‐techniques (differential‐pulse voltammetry viz. DPV and cyclic‐voltammetry viz. CV) in three‐ways simultaneously. The CuO@rGO‐modified‐GCE (CuO@rGO/GCE) exhibits remarkable sensitivity with very low‐detection‐limit of 5–11 nM and long term‐usage, which is far‐better than other reported works. Non‐interfering ability in existence of several body‐interferents exposes that CuO@rGO/GCE could be an effective/ beneficial contrivance for the detection of RFP.