Hydrogen sulfide (H2S) and hydrazine (N2H4) are toxic compounds in environmental and living systems, and hydrogen sulfide is also an important signaling molecule. However, in the absence of dual-color probes capable of detecting both H2S and N2H4, the ability to monitor the crosstalk of these substances is restricted. Herein, we developed an ESIPT-based dual-response fluorescent probe (BDM-DNP) for H2S and N2H4 detection via dually responsive sites. The BDM-DNP possessed absorbing strength in the detection of H2S and N2H4, with a large Stokes shift (156 nm for H2S and 108 nm for N2H4), high selectivity and sensitivity, and good biocompatibility. Furthermore, BDM-DNP can be utilized for the detection of hydrogen sulfide and hydrazine in actual soil, and gaseous H2S and N2H4 in environmental systems. Notably, BDM-DNP can detect H2S and N2H4 in living cells for disease diagnosis and treatment evaluation.