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Cancer represents a prominent health concern on a global scale and stands as a significant contributor to mortality. The accurate quantification of anti-cancer drugs such as paclitaxel in human biofluids is critical for effective treatment and monitoring. In this study, a straightforward one-step hydrothermal method was presented for synthesizing carbon dots (CDs), eliminating the need for any additional decoration or modification, by utilizing combretum micranthum extract as a natural carbon source. A paclitaxel sensor was fabricated by modifying a glassy carbon electrode (GCE) with the green synthesized CDs. At optimal conditions, the CDs-GCE exhibited a linear response for paclitaxel analysis in a range of 0.07 µM to 35 µM, with a low detection limit of 2.1 nM. The suggested sensor indicates acceptable reproducibility for paclitaxel detection ((RSD=2.6 %). In addition, the CDs-GCE depicts a good resistant versus common interfering species including flutamide, dopamine, glucose, nilutamide, lactose, tinidazole, ascorbic acid, and L-cysteine. The applicability of the sensor for paclitaxel detection in human serum and human urine samples was effectively assessed. The presented electrochemical sensing protocol for paclitaxel detection offers several merits, including a low limit of detection, fast response time, resistance to interference, and ease of use.