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The electrochemical detection of dipyridamole (DIPY) is highly essential since it is extensively used for the treatment of cardiovascular diseases and to impart inhibitory effects for cancer patients. In this work, we report the development of a novel composite of MXene and ReS 2 (ReS 2 –Nb 2 CT x ) by hydrothermal method. It was found that Nb 2 CT x was partially oxidized and ReS 2 nanoparticles were distributed on the surface of Nb 2 CT x during the hydrothermal synthesis. The ReS 2 –Nb 2 CT x was used to modify carbon cloth electrodes and used for the electrochemical detection of DIPY. The ratio of ReS 2 was optimized in the composite by varying the atomic ratio from 4 to 9 and it was found that 6ReS 2 –Nb 2 CT x showed the best sensing characteristics owing to the optimum interaction between ReS 2 and Nb 2 CT x . The developed sensor was able to detect DIPY linearly in the range 100 pM–1 μM and achieved a limit of detection of (LOD) of 28 pM. The modified electrode exhibited excellent selectivity towards DIPY in the presence of other interferents in addition to its good storage stability and repeatability. Furthermore, the developed sensor was also used for the detection of DIPY in human serum samples. Thus, this work paves the way to develop MXene-based platform for fabrication of flexible device capable of monitoring the acute levels of DIPY. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s41127-022-00055-x.