Display omitted •A new nanosensor based on BSA capped-CuNCs for MGF detection was developed.•The proposed nanosensor showed excellent performance in sensing of MGF.•The mechanism of the selective recognition of MGF by the CuNCs@BSA sensor was proposed.•The nanosensor was applied in real samples with good recoveries. In this paper we report for the first time a fluorescence nanosensor for the detection of trace amount of mangiferin (MGF) by using bovine serum albumin (BSA)-protected copper nanoclusters (CuNCs@BSA). The CuNCs@BSA have an average size of 1.4±0.2nm and show a blue emission at 640nm. Fluorescence emission of CuNCs@BSA was quenched in the presence of MGF providing a fluorescence responsive probe in a linear range of 3–180μM with a detection limit of 210nM calculated at a signal-to-noise ratio of 3. The CuNCs@BSA show high photostability, since after 50min of irradiation, only a fluorescence decrease of 15% is appreciated. Interference and competition studies indicate that the nanoprobe presents good selectivity over other relevant molecules including flavonoids and metal ions. These results confirmed that the nanosensor has high selectivity towards MGF in the presence of other substances. In addition the mechanism of sensitive fluorescence quenching response of CuNCs@BSA to MGF has been discussed. The sensor was then applied to the analysis of MGF in African mango extract and satisfactory recoveries were obtained indicating a good accuracy and reproducibility of the fluorescence nanosensor for detection of MGF. The proposed sensor is simple, rapid, and cost-effective demonstrating great potential for the determination of MGF in real samples.